Table S1. In silico substrates utilization of B. subtilis networks before and after network expansion and metabolic gap analysis based on high-throughput Biolog phenotyping.

1) From KEGG compound database (http://www.genome.jp)2) See supplementary Bacillus subtilis model excel file. 3) The confidence level on data was determined based on the number of positive reactions out of the 8 measurements (cut-off, 1.2 times of negative control): ++, growth with high-

confidence (all of the 8 measurements showed positive reactions); +, growth with medium-confidence (6 or 7 out of the 8 measurements showed positive reactions); +/-, low-

confident data (3 to 5 out of the 8 measurements showed positive reactions); -, no growth with medium-confidence (1 or 2 out of the 8 measurements showed positive reactions); and

--, no growth with high-confidence (none out of the 8 measurements showed positive reactions).4) Results are scored as + or – meaning growth or no growth determined from in vivo/in silico data. The n represents that corresponding pathway could not be included in the B. subtilis

metabolic network due to unknown pathway(s) or no growth.5) Computed after network expansion. Simulation conditions are detailed in the supplementary Simulation conditions excel file. Threshold value of specific growth rate for cell viability

was assumed to be 10-8 h-1.6) Definitions of the reaction abbreviation are described in supplementary Bacillus subtilis model excel file. Corresponding gene is shown in parenthesis.

  

 No.

 Biolog compound

 KEGG no. 1)

 CAS no.

 Abbr. 2)

 Confidence

level on growthdata 3)

(In vivo/in silico) 4)

 In silico growth

rate (/hr) 5) 

Comment or model refinement 6) 

Reference for cell growth

Before network

expansion

After network

expansionC-source 1 L-Leucine C00123 61-90-5 leu-L -- (-/-) (-/-) 0    

2 L-Lysine C00047 56-87-1 lys-L -- (-/-) (-/-) 0

3 L-Methionine C00073 63-68-3 met-L -- (-/-) (-/-) 0

4 L-Phenylalanine C00079 63-91-2 phe-L -- (-/-) (-/-) 0

5 D,L-Carnitine C0031844985-71-

9 crn -- (-/-) (-/-) 0

6 2,3-Butanediol C0304424347-58-

8 btd-RR - (-/-) (-/-) 2.5736E-09    

7 g-Amino-Butyric Acid C00334 56-12-2 4abut - (-/+) (-/+) 0.26023    

8 Glycine C00037 56-40-6 gly -- (-/n) (-/+) 0.036084 No grwoth, Mortl et al. 2004

9 L-Isoleucine C00407 73-32-5 ile-L -- (-/+) (-/+) 0.42451

10 L-Valine C00183 72-18-4 val-L -- (-/+) (-/+) 0.31494    

11 Tween 20 -- (-/n) (-/n)

12 1,2-Propanediol - (-/n) (-/n)

13 Tween 40 - (-/n) (-/n)

14 Tween 80 -- (-/n) (-/n)

15 a-Hydroxy Glutaric Acid-g-Lactone -- (-/n) (-/n)

16 D-Threonine -- (-/n) (-/n)

17 Tricarballylic Acid -- (-/n) (-/n)

18 Tyramine - (-/n) (-/n)

19 Chondroitin Sulfate C - (-/n) (-/n)

20 Gelatin -- (-/n) (-/n)

21 Laminarin -- (-/n) (-/n)

22 Mannan - (-/n) (-/n)

23 D-Arabitol - (-/n) (-/n)

24 i-Erythritol - (-/n) (-/n)

25 a-Methyl-D-Mannoside - (-/n) (-/n)

26 b-Methyl-D-Xyloside - (-/n) (-/n)

27 Xylitol - (-/n) (-/n) No growth, Chalumeau et al. 1978

28 d-Amino-Valeric Acid - (-/n) (-/n)

29 Caproic Acid -- (-/n) (-/n) No growth, Bryan et al. 1996

30 Citraconic Acid -- (-/n) (-/n)

31 D,L-Citramalic Acid -- (-/n) (-/n)

32 2-Hydroxy-Benzoic Acid -- (-/n) (-/n)

33 4-Hydroxy-Benzoic Acid - (-/n) (-/n)

34 b-Hydroxy-Butyric Acid - (-/n) (-/n)

35 g-Hydroxy-Butyric Acid - (-/n) (-/n)

36 a-Keto-Valeric Acid -- (-/n) (-/n)

37 Itaconic Acid -- (-/n) (-/n)

38 D-Lactic Acid Methyl Ester - (-/n) (-/n)

39 Malonic Acid -- (-/n) (-/n)

40 Oxalic Acid -- (-/n) (-/n)

41 Quinic Acid -- (-/n) (-/n)

42 D-Ribono-1,4-Lactone -- (-/n) (-/n)

43 Sebacic Acid -- (-/n) (-/n)

44 Sorbic Acid -- (-/n) (-/n)

45 Succinamic Acid -- (-/n) (-/n)

46 D-Tartaric Acid - (-/n) (-/n)

47 L-Tartaric Acid -- (-/n) (-/n)

48 Acetamide -- (-/n) (-/n)

49 L-Alaninamide - (-/n) (-/n)

50 N-Acetyl-L-Glutamic Acid -- (-/n) (-/n)

51 L-Homoserine -- (-/n) (-/n)

52 4-Hydroxy-L-Proline (trans) -- (-/n) (-/n)

53 L-Pyroglutamic Acid -- (-/n) (-/n)

54 Butylamine (sec) -- (-/n) (-/n)

55 D,L-Octopamine - (-/n) (-/n)

56 Putrescine -- (-/n) (-/n)

57 2,3-Butanone -- (-/n) (-/n)

58 3-Hydroxy-2-Butanone -- (-/n) (-/n)

59 Formic Acid C00058 64-18-6 for + (+/-) (+/-) 0 In silico, NADH and ATP production  

60 Acetic Acid C00033 64-19-7 ac ++ (+/-) (+/-) 0 In silico, NADH and ATP production no growth, Bryan 1996

61 Acetoacetic Acid C00164 541-50-4 acac ++ (+/n) (+/-) 7.5308E-11 In silico, NADH and ATP production; ACACt6  

62 L-Arabinose C00259 147-81-9 arab-L + (+/+) (+/+) 0.33294 Growth, Strauch 1995

63 N-Acetyl-D-Glucosamine C00140 7512-17-6 acgam ++ (+/+) (+/+) 0.53762 Growth, Mobley et al. 1982

64 D-Saccharic Acid C00818 87-73-0 glcr ++ (+/-) (+/+) 0.28091 HOXPRX (ykwC) Growth, Hosoya et al. 2002

65 Succinic Acid C00042 110-15-6 succ ++ (+/+) (+/+) 0.19961 Growth, Schuch et al. 1999

66 D-Galactose C00124 59-23-4 gal ++ (+/+) (+/+) 0.40713 Growth, Mobley et al. 1982

67 L-Aspartic Acid C00049 56-84-8 asp-L ++ (+/+) (+/+) 0.17629Growth, Whiteman et al. 1980 and Sonenshein 2002

68 L-Proline C00148 147-85-3 pro-L ++ (+/+) (+/+) 0.34439 Growth, Sonenshein 2002

69 D-Alanine C00133 338-69-2 ala-D ++ (+/+) (+/+) 0.16716 Growth, Mortl et al. 2004

70 D-Trehalose C01083 99-20-7 tre ++ (+/+) (+/+) 0.62418

71 D-Mannose C00159 3458-28-4 man ++ (+/+) (+/+) 0.41177 Growth, Mobley et al. 1982

72 Dulcitol C01697 608-66-2 galt ++ (+/-) (+/+) 0.44262 GALTpts, GLTPD (yjmD), TGBPA

73 D-Serine C00740 312-84-5 ser-D ++ (+/n) (+/+) 0.13536 SER_Dt6

74 D-Sorbitol C00794 50-70-4 sbt-D ++ (+/+) (+/+) 0.43959 Growth, Watanabe et al. 2003

75 Glycerol C00116 56-81-5 glyc ++ (+/+) (+/+) 0.22085 Growth, Mobley et al. 1982

76 D-Glucuronic Acid C00191 6556-12-3 glcur ++ (+/+) (+/+) 0.32712 Growth, Mekjian et al. 1999

77 D-Gluconic Acid C00257 526-95-4 glcn-D ++ (+/+) (+/+) 0.37004

78 D,L-a-Glycerol- Phosphate C00093 57-03-4 glyc3p ++ (+/-) (+/+) 0.23933 Pit2 (irreversible) -->Pit6 (reversible) Growth, Beijer et al. 1993

79 D-Xylose C00181 58-86-6 xyl-D ++ (+/+) (+/+) 0.33294 Growth, Ozcengiz et al. 1990

80 L-Lactic Acid C00186 79-33-4 lac-L ++ (+/+) (+/+) 0.16716

81 D-Mannitol C00392 69-65-8 mnl ++ (+/+) (+/+) 0.44423 Growth, Watanabe et al. 2003

82 L-Glutamic Acid C00025 56-86-0 glu-L ++ (+/+) (+/+) 0.28355 Growth, Sonenshein 2002

83 D-Glucose-6-Phosphate C00092 56-73-5 g6p ++ (+/n) (+/+) 0.42568 G6Pt6_2

84 D,L-Malic Acid C00149 97-67-6 mal-L ++ (+/+) (+/+) 0.17629 Growth, Markuszewski et al. 2003

85 D-Ribose C00121 50-69-1 rib-D ++ (+/+) (+/+) 0.31903 Growth, Mobley et al. 1982

86 L-Rhamnose C00507 3615-41-6 rmn + (+/n) (+/+) 0.41952 RMNt, RMPA

87 D-Fructose C00095 57-48-7 fru ++ (+/+) (+/+) 0.41028 Growth, Besson et al. 1987

88 a-D-Glucose C00031 50-99-7 glc-D ++ (+/+) (+/+) 0.41177 Growth, Markuszewski et al. 2003

89 Maltose C00208 69-79-4 malt ++ (+/+) (+/+) 0.62418 Growth, Tangney et al. 1992

90 D-Melibiose C05402 585-99-9 melib ++ (+/n) (+/+) 0.62418 MELIBt2

91 Thymidine C00214 50-89-5 thymd ++ (+/-) (+/+) 0.36024 THMt2 (irreversible) --> THMt6 (reversible) Growth, Schuch et al. 1999

92 L-Asparagine C00152 70-47-3 asn-L ++ (+/+) (+/+) 0.17658 Growth, Sonenshein 2002

93 a-Keto-Glutaric Acid C00026 328-50-7 akg + (+/+) (+/+) 0.25091 Growth, Fournier et al. 1972

94 Sucrose C00089 57-50-1 sucr ++ (+/+) (+/+) 0.62418 Growth, Mobley et al. 1982

95 Uridine C00299 58-96-8 uri ++ (+/-) (+/+) 0.35878 URAt2 (irreversible) --> URAt6 (reversible)

96 L-Glutamine C00064 56-85-9 gln-L ++ (+/+) (+/+) 0.27121

97 D-Glucose-1-Phosphate C00103 59-56-3 g1p ++ (+/n) (+/+) 0.42568 G1Pt6_2

98 D-Fructose-6-Phosphate C00085 643-13-0 f6p ++ (+/n) (+/+) 0.42568 F6Pt6

99 b-Methyl-D-Glucoside25360-07-

0 mbdg ++ (+/+) (+/+) 0.41177

100 Maltotriose C01835 1109-28-0 malttr ++ (+/+) (+/+) 0.62418

101 2`-Deoxy-Adenosine C00559 958-09-8 dad-2 ++ (+/-) (+/+) 0.51626 XANt2 (irreversible) --> XANt6 (reversible)

102 Adenosine C00212 58-61-7 adn ++ (+/-) (+/+) 0.51333 XANt2 (irreversible) --> XANt6 (reversible)

103 Citric Acid C00158 77-92-9 cit + (+/+) (+/+) 0.28822 Growth, Warner and Lolkema 2002

104 Fumaric Acid C00122 110-17-8 fum ++ (+/+) (+/+) 0.17629 Growth, Warner and Lolkema 2002

105 Propionic Acid C00163 79-09-4 ppa + (+/n) (+/+) 0.1717 PPAt6

106 Mucic Acid C00879 526-99-8 galctr-D ++ (+/-) (+/+) 0.28091 HOXPRx (ykwC) Growth, Hosoya et al. 2002

107 Glycolic Acid C00160 79-14-1 glyclt + (+/n) (+/+) 0.036038 HOXPRX (ykwC), GLXCBL, GLYCLTt2ir

108 Glyoxylic Acid C00048 298-12-4 glx + (+/n) (+/+) 0.036038 HOXPRX (ykwC), GLXCBL, GLXt2

109 D-Cellobiose C00185 cellb ++ (+/+) (+/+) 0.62418

110 Inosine C00294 58-63-9 ins ++ (+/-) (+/+) 0.50794 XANt2 (irreversible) --> XANt6 (reversible)

111 L-Serine C00065 56-45-1 ser-L ++ (+/+) (+/+) 0.13632

112 L-Threonine C00188 72-19-5 thr-L ++ (+/+) (+/+) 0.20918

113 L-Alanine C00041 56-41-7 ala-L + (+/+) (+/+) 0.16716

114 N-Acetyl-b-D-Mannosamine C00645 3615-17-6 acmana + (+/n) (+/+) 0.57569

UAGDP (irreversible) -> UAGDPr (reversible),G1PACT (irreversible) -> G1PACTr (reversible), ACMANAt2

115 D-Malic Acid C00497 636-61-3 mal-D ++ (+/n) (+/+) 0.1717 ME1x_D (ycsA), Mal_Dt2 No growth, Warner and Lolkema 2002

116 L-Malic Acid C00149 97-67-6 mal-L ++ (+/+) (+/+) 0.17629 Growth, Markuszewski et al. 2003

117 Pyruvic Acid C00022 127-17-3 pyr + (+/+) (+/+) 0.13536 Growth, Nakano et al. 1997

118 D-Galacturonic Acid C00333 685-73-4 galur ++ (+/+) (+/+) 0.32712 Growth, Mekjian et al. 1999

119 Dextrin C00721 9004-53-9 dextrin ++ (+/n) (+/+) 0.62418 MLTG6, DEXTRINt2

120 Glycogen C00182 glycogen ++ (+/n) (+/+) 0.43032 GLYCOGENt

121 N-Acetyl-Neuraminic Acid C00270 131-48-6 acnam ++ (+/n) (+/+) 0.77259 ACNPLYSr (spsE), ACNAMt2

122 D-Arabinose C0021610323-20-

3 arab-D ++ (+/n) (+/+) 0.33758 ARABI, arab-Dt Growth, Strauch et al. 1995

123 L-Arabitol C00532 7643-75-6 abt-L + (+/n) (+/+) 0.37004 ARABRr (yvgN and ytbE), ABTt

124 Arbutin C06186 497-76-7 arbt ++ (+/-) (+/+) 0.41641 HQNt6 Growth, Kruger and Hecker 1995

125 2-Deoxy-D-Ribose C01801 533-67-5 drib ++ (+/+) (+/+) 0.32257 Growth, Schuch et al. 1999

126 Palatinose C0174213718-94-

0 pala ++ (+/n) (+/+) 0.62418 ISOMS, PALAt2

127 D-Raffinose C00492 512-69-6 raffin ++ (+/n) (+/+) 0.62418 RAFFINt2

128 Salicin C01451 138-52-3 salcn ++ (+/n) (+/+) 0.41641 2HXMPt6 Growth, Kruger and Hecker 1995

129 L-Sorbose C00247 87-79-6 srb-L + (+/n) (+/+) 0.41318 SORD_D, SRB_Lt

130 D-Glucosamine C00329 3416-24-8 gam ++ (+/+) (+/+) 0.41227 Growth, Mobley et al. 1982

131 L-Ornithine C01602 70-26-8 orn-L + (+/+) (+/+) 0.34463 Growth, Sonenshein 2002

132 Dihydroxy-Acetone C00184 96-26-4 dha + (+/n) (+/+) 0.20699ALKP (irreversible) --> ALKPr (reversible), DHAt

133 L-Fucose       ++ (+/n) (+/n)   Pathway is not well understood  

134 D-Galactonic Acid-g-Lactone ++ (+/n) (+/n) Pathway is not well understood

135 a-Methyl-D-Galactoside ++ (+/n) (+/n) Pathway is not well understood

136 m-Tartaric Acid + (+/n) (+/n) Pathway is not well understood

137 Glycyl-L-Aspartic Acidgly-asp-

L ++ (+/n) (+/n) DIPEPabc13 (only transporter)

138 Glycyl-L-Glutamic Acidgly-glu-

L ++ (+/n) (+/n) DIPEPabc10 (only transporter)

139 L-Alanyl-Glycine 687-69-4 L-alagly ++ (+/n) (+/n) DIPEPabc4 (only transporter)

140 Glycyl-L-Proline 704-15-4gly-pro-

L ++ (+/n) (+/n) DIPEPabc14 (only transporter)

141 D-Psicose ++ (+/n) (+/n) Pathway is not well understood

142 Glucuronamide ++ (+/n) (+/n) Pathway is not well understood

143 L-Galactonic Acid-g-Lactone ++ (+/n) (+/n) Pathway is not well understood

144 a-Cyclodextrin + (+/n) (+/n) Pathway is not well understood

145 g-Cyclodextrin ++ (+/n) (+/n) Pathway is not well understood

146 b-D-Allose ++ (+/n) (+/n) Pathway is not well understood

147 Amygdalin ++ (+/n) (+/n) Pathway is not well understood

148 3-0-b-D-Galactopyranosyl-D-Arabinose ++ (+/n) (+/n) Pathway is not well understood

149 Gentiobiose ++ (+/n) (+/n) Pathway is not well understood

150 Maltitol + (+/n) (+/n) Pathway is not well understood

151 b-Methyl-D-Glucuronic Acid + (+/n) (+/n) Pathway is not well understood

152 Turanose + (+/n) (+/n) Pathway is not well understood

153 5-Keto-D-Gluconic Acid       + (+/n) (+/n)   Pathway is not well understood  

154 a-D-Lactose C00243 63-42-3 lcts +/- 0.62418 Growth, Chaudhuri et al. 1982

155 m-Inositol C00137 87-89-8 inost +/- 0.38718 Growth, Yoshida et al. 2002

156 L-Arginine C00062 74-79-3 arg-L +/- 0.35563 Growth, Sonenshein 2002

157 L-Histidine C00135 71-00-1 his-L +/- 0.32176 Growth, Sonenshein 2002

158 D-Aspartic Acid +/-

159 D-Glucosaminic Acid +/-

160 a-Keto-Butyric Acid +/-

161 Lactulose +/-

162 a-Hydroxy-Butyric Acid +/-

163 Adonitol +/-

164 Bromo-Succinic Acid +/-

165 Mono Methyl Succinate +/-

166 Methyl Pyruvate +/-

167 p-Hydroxy-Phenylacetic Acid +/-

168 m-Hydroxy-Phenylacetic Acid +/-

169 L-Lyxose +/-

170 b-Phenylethylamine +/-

171 Ethanolamine +/-

172 b-Cyclodextrin +/-

173 Inulin +/-

174 Pectin +/-

175 N-Acetyl-D-Galactosamine +/-

176 D-Fucose +/-

177 L-Glucose +/-

178 D-Lactitol +/-

179 D-Melezitose +/-

180 a-Methyl-D-Glucoside +/-

181 b-Methyl-D-Galactoside +/-

182 3-O-Methyl-Glucose +/-

183 Sedoheptulosan +/-

184 Stachyose +/-

185 D-Tagatose +/-

186 N-Acetyl-D-Glucosaminitol +/-

187 Butyric Acid +/-

188 Capric Acid +/-

189 Melibionic Acid +/-

190 Oxalomalic Acid +/-N-source 1 Thymine C00178 65-71-4 thym - (-/-) (-/-) 0   No growth, Fisher and Debarobuille 2002

2 Uracil C00106 66-22-8 ura - (-/-) (-/-) 0 No growth, Fisher and Debarobuille 2002

3 Uridine C00299 58-96-8 uri - (-/-) (-/-) 0    

4 Adenine C00147 73-24-5 ade - (-/+) (-/+) 0.7424   Growth, Fisher and Debarobuille 2002

5 Inosine C00294 58-63-9 ins - (-/+) (-/+) 1.1289    

6 Biuret       - (-/n) (-/n)      

7 Agmatine - (-/n) (-/n)

8 Acetamide - (-/n) (-/n)

9 N-Acetyl-D-Galactosamine - (-/n) (-/n)

10 d-Amino-N-Valeric Acid - (-/n) (-/n)

11 a-Amino-N-Valeric Acid       - (-/n) (-/n)      

12 L-Cysteine C00097 52-90-4 cys-L ++ (+/-) (+/-) 0   No growth, Fisher and Debarobuille 2002

13 L-Methionine C00073 63-68-3 met-L + (+/-) (+/-) 0   No growth, Fisher and Debarobuille 2002

14 Ammonia C01342 nh4 ++ (+/+) (+/+) 0.5833 Growth, Fisher and Debarobuille 2002

15 Urea C00086 57-13-6 urea + (+/+) (+/+) 0.5926 Growth, Fisher and Debarobuille 2002

16 L-Alanine C00041 56-41-7 ala-L + (+/+) (+/+) 0.6242 Growth, Fisher and Debarobuille 2002

17 L-Arginine C00062 74-79-3 arg-L ++ (+/+) (+/+) 0.9845 Growth, Baumberg and Harwood 1979

18 L-Asparagine C00152 70-47-3 asn-L ++ (+/+) (+/+) 0.8008 Growth, Besson et al. 1987

19 L-Aspartic Acid C00049 56-84-8 asp-L ++ (+/+) (+/+) 0.6242 Growth, Ozcengiz et al. 1990

20 L-Glutamic Acid C00025 56-86-0 glu-L + (+/+) (+/+) 0.6242 Growth, Ozcengiz et al. 1990

21 L-Glutamine C00064 56-85-9 gln-L ++ (+/+) (+/+) 0.8986 Growth, Baumberg and Harwood 1979

22 Glycine C00037 56-40-6 gly + (+/n) (+/+) 0.6242

23 L-Proline C00148 147-85-3 pro-L ++ (+/+) (+/+) 0.6242 Growth, Baumberg and Harwood 1979

24 L-Serine C00065 56-45-1 ser-L ++ (+/+) (+/+) 0.6242 Growth, Besson, 1987

25 L-Threonine C00188 72-19-5 thr-L + (+/+) (+/+) 0.6242 Growth, Fisher and Debarobuille 2002

26 L-Valine C00183 72-18-4 val-L + (+/+) (+/+) 0.6242 Growth, Fisher and Debarobuille 2002

27 D-Alanine C00133 338-69-2 ala-D ++ (+/+) (+/+) 0.6242 Growth, Mortl et al. 2004

28 D-Glutamic Acid C00217 56-86-0 glu-D + (+/n) (+/+) 0.6242 GLU-Dt2

29 L-Citrulline C00327 372-75-8 citr-L + (+/n) (+/+) 0.9467 CITR_Lt2

30 L-Ornithine C01602 70-26-8 orn-L + (+/+) (+/+) 0.9693 Growth, Fisher and Debarobuille 2002

31 Ethanolamine C00189 141-43-5 etha ++ (+/-) (+/+) 0.6242 ETHAAL

32 D-Glucosamine C00329 3416-24-8 gam ++ (+/+) (+/+) 0.6242 Growth, Fisher and Debarobuille 2002

33 N-Acetyl-D-Glucosamine C00140 7512-17-6 acgam + (+/+) (+/+) 0.6242

34 Cytidine C00475 65-46-3 cytd ++ (+/-) (+/+) 0.6438ACACt2, URAt2 (irreversible) -> URAt6 (reversible)

35 Xanthine C00385 69-89-6 xan ++ (+/-) (+/+) 0.7032 ALLTAHr, UGLYCHr Growth, Fisher and Debarobuille 2002

36 Uric Acid C00366 69-93-2 urate + (+/-) (+/+) 0.6668 ALLTAHr, UGLYCHr Growth, Fisher and Debarobuille 2002

37 g-Amino-N-Butyric Acid C00334 56-12-2 4abut + (+/+) (+/+) 0.6242 Growth, Fisher and Debarobuille 2002

38 L-Pyroglutamic Acid       ++ (+/n) (+/n)   Pathway is not well understood  

39 Ethylenediamine + (+/n) (+/n) Pathway is not well understood

40 b-Phenylethylamine + (+/n) (+/n) Pathway is not well understood

41 D-Mannosamine + (+/n) (+/n) Pathway is not well understood

42 Ala-Aspala-L-asp-L + (+/n) (+/n) DIPEPabc1 (only transporter)

43 Ala-Glnala-L-gln-L ++ (+/n) (+/n) DIPEPabc2 (only transporter)

44 Ala-Glu13187-90-

1ala-L-glu-L + (+/n) (+/n) DIPEPabc3 (only transporter)

45 Ala-Gly 687-69-4 L-alagly + (+/n) (+/n) DIPEPabc4 (only transporter)

46 Ala-His 3253-17-6ala-L-his-L ++ (+/n) (+/n) DIPEPabc5, MEAMP1(ala-his)

47 Ala-Leu 3303-34-2ala-L-leu-L + (+/n) (+/n) DIPEPabc6 (only transporter)

48 Ala-Thrala-L-Thr-L ++ (+/n) (+/n) DIPEPabc7 (only transporter)

49 Gly-Asn 1999-33-3gly-asn-

L ++ (+/n) (+/n) DIPEPabc8 (only transporter)

50 Gly-Gln13115-71-

4gly-gln-

L ++ (+/n) (+/n) DIPEPabc9 (only transporter)

51 Gly-Glugly-glu-

L + (+/n) (+/n) DIPEPabc10 (only transporter)

52 Gly-Met 554-94-9gly-met-

L + (+/n) (+/n) DIPEPabc11 (only transporter)

53 Met-Ala    met-L-ala-L + (+/n) (+/n)   DIPEPabc12 (only transporter)  

54 Nitrite C00088 7697-37-2 no2 +/- 0.5079 Growth, Fisher and Debarobuille 2002

55 Nitrate C00244 no3 +/- 0.492 Growth, Fisher and Debarobuille 2002

56 L-Histidine C00135 71-00-1 his-L +/- 0.947 Growth, Fisher and Debarobuille 2002

57 L-Isoleucine C00407 73-32-5 ile-L +/- 0.6242 Growth, Fisher and Debarobuille 2002

58 L-Lysine C00047 56-87-1 lys-L +/- 0 No growth, Fisher and Debarobuille 2002

59 L-Tryptophan C00078 73-22-3 trp-L +/- 0 No growth, Fisher and Debarobuille 2002

60 D-Serine C00740 312-84-5 ser-D +/- 0.6242 No growth, Fisher and Debarobuille 2002

61 Guanosine C00387 118-00-3 gsn +/- 1.1019 Growth, Fisher and Debarobuille 2002

62 Allantoin C01551 97-59-6 alltn +/- 0.6668 Growth, Fisher and Debarobuille 2002

63 L-Leucine +/-

64 L-Phenylalanine +/-

65 L-Tyrosine +/-

66 D-Asparagine +/-

67 D-Aspartic Acid +/-

68 D-Lysine +/-

69 D-Valine +/-

70 L-Homoserine +/-

71 N-Acetyl-D,L-Glutamic Acid +/-

72 N-Phthaloyl-L-Glutamic Acid +/-

73 Hydroxylamine +/-

74 Methylamine +/-

75 N-Amylamine +/-

76 N-Butylamine +/-

77 Ethylamine +/-

78 Putrescine +/-

79 Histamine +/-

80 Tyramine +/-

81 Formamide +/-

82 Glucuronamide +/-

83 D,L-Lactamide +/-

84 D-Galactosamine +/-

85 N-Acetyl-D-Mannosamine +/-

86 Adenosine +/-

87 Cytosine +/-

88 Guanine +/-

89 Thymidine +/-

90 Xanthosine +/-

91 Alloxan +/-

92 Parabanic Acid +/-

93 D,L-a-Amino-N-Butyric Acid +/-

94 e-Amino-N-Caproic Acid +/-

  95 D,L-a-Amino-Caprylic Acid       +/-          P-source 1 Methylene Diphosphonic Acid       - (-/n) (-/n)      

2 Thymidine 3’,5’- Cyclic Monophosphate     - (-/n) (-/n)      

3 Phosphate C0000914265-44-

2 pi ++ (+/+) (+/+) 0.5833 Growth, Baumberg and Harwood 1979

4 Pyrophosphate C00013 2466-09-3 ppi + (+/+) (+/+) 0.5821

5 Trimetaphosphate C02466 6893-02-3 tmp + (+/n) (+/+) 0.5973 ADK2 (adk), TMPHi, TMPt6

6 Adenosine- 3’-Monophosphate C01367 84-21-9 3amp ++ (+/n) (+/+) 1.1398 3AMPt6

7 Adenosine- 5’-Monophosphate C00020 61-19-8 amp ++ (+/n) (+/+) 1.1405 AMPt6

8 D,L-a-Glycerol Phosphate C00093 57-03-4 glyc3p + (+/+) (+/+) 0.6242

9 D-2-Phospho-Glyceric Acid C00631 2pg + (+/n) (+/+) 0.6242 2PGt6

10 D-3-Phospho-Glyceric Acid C00197 3pg + (+/n) (+/+) 0.6242 3PGt6

11 Guanosine- 3’-Monophosphate C01801 533-67-5 3gmp + (+/n) (+/+) 1.1065 3GMPt6

12 Guanosine- 5’-Monophosphate C00144 85-32-5 gmp + (+/n) (+/+) 1.1359 GMPt6

13 Phosphoenol Pyruvate C00074 138-08-9 pep + (+/n) (+/+) 0.6242 PEPt6

14 Phospho-Glycolic Acid C0304424347-58-

8 2pglyc + (+/n) (+/+) 0.6242 PGLYCP (yhcW), 2PGLYCt6

15 D-Glucose-1-Phosphate C00103 59-56-3 g1p + (+/n) (+/+) 0.6242 G1Pt6_2

16 D-Glucose-6-Phosphate C00092 56-73-5 g6p + (+/n) (+/+) 0.6242 G6Pt6_2

17 D-Glucosamine-6-Phosphate C00352 3616-42-0 gam6p + (+/n) (+/+) 1.053 GAM6Pt

18 6-Phospho-Gluconic Acid C00345 6pgc ++ (+/n) (+/+) 0.6242 6PGCt6

19 Cytidine- 3’- Monophosphate C00559 958-09-8 3cmp + (+/n) (+/+) 0.9897 3CMPt6

20 Cytidine- 5’- Monophosphate C00055 84-52-6 cmp + (+/n) (+/+) 0.9901 CMPt6

21 D-Mannose-1-Phosphate C03812 man1p ++ (+/n) (+/+) 0.6242 MAN1Pt6

22 D-Mannose-6-Phosphate C00275 man6p + (+/n) (+/+) 0.6242 MAN6pt6

23 Phospho-L-Arginine C05945 1189-11-3 argp + (+/n) (+/+) 1.008 ARGKr (mcsB), ARGPt6

24 O-Phospho-D-Serine C02532 pser-D + (+/n) (+/+) 0.7595 PSER_Dt6

25 O-Phospho-L-Serine C01005 407-41-0 pser-L + (+/n) (+/+) 0.7781 PSER_Lt6

26 Uridine- 3’- Monophosphate C0136835170-03-

7 3ump + (+/n) (+/+) 0.6438 3UMPt6

27 Uridine- 5’- Monophosphate C00105 58-97-9 ump + (+/n) (+/+) 0.6438 UMPt6

28 Thymidine- 5’-Monophosphate C00364 365-07-1 dtmp + (+/n) (+/+) 0.6278THMt2 (irreversible) -->THMt6 (reversible), DTMPt6  

29 Tripolyphosphate + (+/n) (+/n) Pathway is not well understood

30 Adenosine- 2’-Monophosphate + (+/n) (+/n) Pathway is not well understood

31 Adenosine- 2’,3’-Cyclic Monophosphate ++ (+/n) (+/n) Pathway is not well understood

32 Thiophosphate ++ (+/n) (+/n) Pathway is not well understood

33 Dithiophosphate ++ (+/n) (+/n) Pathway is not well understood

34 b-Glycerol Phosphate + (+/n) (+/n) Pathway is not well understood

35 Carbamyl Phosphate + (+/n) (+/n) Pathway is not well understood

36 Guanosine- 2’-Monophosphate + (+/n) (+/n) Pathway is not well understood

37 2-Deoxy-D-Glucose 6-Phosphate + (+/n) (+/n) Pathway is not well understood

38 Cytidine- 2’- Monophosphate + (+/n) (+/n) Pathway is not well understood

39 Cytidine- 2’,3’-Cyclic Monophosphate + (+/n) (+/n) Pathway is not well understood

40 Cysteamine-S-Phosphate + (+/n) (+/n) Pathway is not well understood

41 O-Phospho-L-Threonine + (+/n) (+/n) Pathway is not well understood

42 Uridine- 2’- Monophosphate + (+/n) (+/n) Pathway is not well understood

43 Uridine- 2’,3’- Cyclic Monophosphate + (+/n) (+/n) Pathway is not well understood\

44 Phosphoryl Choline + (+/n) (+/n) Pathway is not well understood

45 O-Phosphoryl-Ethanolamine + (+/n) (+/n) Pathway is not well understood

46 Thymidine- 3’-Monophosphate + (+/n) (+/n) Pathway is not well understood

47 Inositol Hexaphosphate       ++ (+/n) (+/n)   Pathway is not well understood  

48 Triethyl Phosphate +/-

49 Hypophosphite +/-

50 Adenosine- 3’,5’-Cyclic Monophosphate +/-

51 Guanosine- 2’,3’-Cyclic Monophosphate +/-

52 Guanosine- 3’,5’-Cyclic Monophosphate +/-

53 Cytidine- 3’,5’-Cyclic Monophosphate +/-

54 Uridine- 3’,5’- Cyclic Monophosphate +/-

55 O-Phospho-D-Tyrosine +/-

56 O-Phospho-L-Tyrosine +/-

57 Phosphocreatine +/-

58 Phosphono Acetic Acid +/-

  59 2-Aminoethyl Phosphonic Acid       +/-          S-source 1 Glutathione C00127   gthox - (-/-) (-/-) 0   `

2 D-Methionine C00855 348-67-4 met-D -- (-/-) (-/-) 0    

3 Sulfate C00059 7664-93-9 so4 - (-/+) (-/+) 0.5833   Growth, van der Ploeng et al. 1998

4 L-Methionine Sulfoxide C02989 metox - (-/+) (-/+) 0.5919 Growth, van der Ploeng et al. 1998

5 Methane Sulfonic Acid   75-75-2 mso3 - (-/+) (-/+) 0.585   Growth, van der Ploeng et al. 1998

6 D-Cysteine - (-/n) (-/n)

7 Cysteamine - (-/n) (-/n)

8 L-Cysteine Sulfinic Acid -- (-/n) (-/n)

9 N-Acetyl-L-Cysteine -- (-/n) (-/n)

10 D,L-Ethionine -- (-/n) (-/n)

11 L-Methionine Sulfone -- (-/n) (-/n)

12 Thiourea -- (-/n) (-/n)

13 1-Thio-b-D-Glucose -- (-/n) (-/n)

14 Hypotaurine - (-/n) (-/n)

15 p-Amino Benzene Sulfonic Acid -- (-/n) (-/n)

16 2-Hydroxyethane Sulfonic Acid - (-/n) (-/n)

17 Tetramethylene Sulfone -- (-/n) (-/n)

18 L-Djenkolic Acid C08275 498-59-9 djenk + (+/n) (+/n)  Only transporter; Pathway is not well understood Growth, van der Ploeng et al. 1998

19 L-Cysteine C00097 52-90-4 cys-L +/- 0.5899 Growth, van der Ploeng et al. 1998

20 L-Cysteinyl-Glycine C0141919246-18-

5 cgly +/-

21 L-Cysteic Acid C0050613100-82-

8 Lcyst +/- 0.5862 Growth, van der Ploeng et al. 1998

22 L-Methionine C00073 63-68-3 met-L +/- 0.5926 Growth, Sekowska and Danchin 2002

23 Taurine C00245 107-35-7 taur +/- 0.5862 Growth, van der Ploeng et al. 1998

24 Butane Sulfonic Acid 2386-54-1 buts +/- 0.5909 Growth, van der Ploeng et al. 1998

25 Thiosulfate +/-

26 Tetrathionate +/-

27 Thiophosphate +/-

28 Dithiophosphate +/-

29 S-Methyl-L-Cysteine +/-

30 Cystathionine +/-

31 Lanthionine 3183-08-2 +/-

32 Glycyl-L-Methionine +/-

33 N-Acetyl-D,L-Methionine +/-

34 D,L-Lipoamide +/-

  35 Taurocholic Acid       +/-          

Reference

Baumberg S, Harwood CR (1979) Carbon and nitrogen repression of arginine catabolic enzymes in Bacillus subtilis. J Bacteriol 137: 189-96.

Beijer L, Nilsson RP, Holmberg C, Rutberg L (1993) The glpP and glpF genes of the glycerol regulon in Bacillus subtilis. J Gen Microbiol 139: 349-59.

Besson F, Chevanet C, Michel G (1987) Influence of the culture medium on the production of iturin A by Bacillus subtilis. J Gen Microbiol 133: 767-72.

Bryan EM, Beall BW, Moran CP Jr (1996) A sigma E dependent operon subject to catabolite repression during sporulation in Bacillus subtilis. J Bacteriol 178: 4778-86.

Chaudhuri A, Mishra AK, Nanda G (1982) Variation of antimetabolite sensitivity with different carbon sources in Bacillus subtilis. Folia Microbiol 27: 73-6.

Chalumeau H, Delobbe A, Gay P (1978) Biochemical and genetic study of D-glucitol transport and catabolism in Bacillus subtilis. J Bacteriol 134: 920-8.

Fisher SH, Debarobuille M. Nitrogen source utilization and its regulation. In A. L. Sonenshein, J. A. Hoch, and R. Losick (eds.), Bacillus subtilis and its closest relatives. From genes

to cells. American Society of Microbiology, Washington, D.C. p181-91.

Fournier RE, McKillen MN, Pardee AB, Willecke K (1972) Transport of dicarboxylic acids in Bacillus subtilis. Inducible uptake of L-malate. J Biol Chem 247: 5587-95.

Hosoya S, Yamane K, Takeuchi M, Sato T (2002) Identification and characterization of the Bacillus subtilis D-glucarate/galactarate utilization operon ycbCDEFGHJ. FEMS

Microbiol Lett 210: 193-199.

Kruger S, Hecker M (1995) Regulation of the putative bglPH operon for aryl-beta-glucoside utilization in Bacillus subtilis. J Bacteriol 177: 5590-7.

Markuszewski MJ, Otsuka K, Terabe S, Matsuda K, Nishioka T (2003) Analysis of carboxylic acid metabolites from the tricarboxylic acid cycle in Bacillus subtilis cell extract by

capillary electrophoresis using an indirect photometric detection method. J Chromatogr A 1010: 113-21.

Mekjian KR, Bryan EM, Beall BW, Moran CP Jr (1999) Regulation of hexuronate utilization in Bacillus subtilis. J Bacteriol 181: 426-33.

Mobley HL, Doyle RJ, Streips UN, Langemeier SO (1982) Transport and incorporation of N-acetyl-D-glucosamine in Bacillus subtilis. J Bacteriol 150: 8-15.

Mortl M, Diederichs K, Welte W, Molla G, Motteran L, Andriolo G, Pilone MS, Pollegioni L (2004) Structure-function correlation in glycine oxidase from Bacillus subtilis. J Biol

Chem 279: 29718-27.

Nakano MM, Dailly YP, Zuber P, Clark DP (1997) Characterization of anaerobic fermentative growth of Bacillus subtilis: identification of fermentation end products and genes

required for growth. J Bacteriol 179: 6749-55.

Ozcengiz G, Alaeddinoglu NG, Demain AL (1990) Regulation of biosynthesis of bacilysin by Bacillus subtilis. J Ind Microbiol 6: 91-100.

Schuch R, Garibian A, Saxild HH, Piggot PJ, Nygaard P (1999) Nucleosides as a carbon source in Bacillus subtilis: characterization of the drm-pupG operon. Microbiology 145: 2957-

66.

Sekowska A, Danchin A (2002) The methionine salvage pathway in Bacillus subtilis. BMC Microbiol 2: 8.

Sonenshein AL (2002) The Krebs citric acid cycle. In A. L. Sonenshein, J. A. Hoch, and R. Losick (eds.), Bacillus subtilis and its closest relatives. From genes to cells. American

Society of Microbiology, Washington, D.C. p151-62.

Strauch MA (1995) AbrB modulates expression and catabolite repression of a Bacillus subtilis ribose transport operon. J Bacteriol 177: 6727-31.

Tangney M, Buchanan CJ, Priest FG, Mitchell WJ (1992) Maltose uptake and its regulation in Bacillus subtilis. FEMS Microbiol Lett 76: 191-6.

van der Ploeg JR, Cummings NJ, Leisinger T, Connerton IF (1998) Bacillus subtilis genes for the utilization of sulfur from aliphatic sulfonates. Microbiology 144: 2555-61.

Warner JB, Lolkema JS (2002) Growth of Bacillus subtilis on citrate and isocitrate is supported by the Mg2+-citrate transporter CitM. Microbiology 148: 3405-12.

Watanabe S, Hamano M, Kakeshita H, Bunai K, Tojo S, Yamaguchi H, Fujita Y, Wong SL, Yamane K (2003) Mannitol-1-phosphate dehydrogenase (MtlD) is required for mannitol

and glucitol assimilation in Bacillus subtilis: possible cooperation of mtl and gut operons. J Bacteriol 185: 4816-24.

Whiteman P, Marks C, Freese E (1980) The sodium effect of Bacillus subtilis growth on aspartate. J Gen Microbiol 119: 493-504.

Yoshida K, Yamamoto Y, Omae K, Yamamoto M, Fujita Y (2002) Identification of two myo-inositol transporter genes of Bacillus subtilis. J Bacteriol 184: 983-91.

Table S2. List of the reactions and genes identified by high-throughput substrate utilization experiments and network gap analysis.

1) See supplementary Bacillus subtilis model excel file for detailed equations.

Subsystem Reaction name 1) Protein Classification Locus name CommentAmino acids and related molecules (4) ATP:L-arginine N-phosphotransferase

cytosine 5-methyltransferase EC-2.1.1.37 BG126275-deoxyribos-5-ylhomocysteinasesulfinoalanine decarboxylase EC-4.1.1.29

Carbohydrates and related molecules (16) N-Acetylneuraminate pyruvate-lyase EC-4.1.3.19arabinose isomerase EC-5.3.1.3ethanolamine ammonia-lyase EC-4.3.1.7formamidase EC-3.5.1.495-dehydro-4-deoxyglucarate aldolase EC-4.1.2.20isomaltulose synthase EC-5.4.99.11Maltodextrin glucosidase (dextrin) BG12421Rhamnulose-1-phosphate aldolase EC-4.1.2.19D-sorbitol dehydrogenase EC-1.1.99.21Tagatose-bisphosphate aldolase EC-4.1.2.40Ureidoglycolate hydrolase EC-3.5.3.19

arabinose reductase EC-1.1.1.21 BG13826, BG14096See Table 1 for more details

Galactitol-1-phosphate dehydrogenase EC-Undetermined BG13207See Table 1 for more details

glyoxalate carboligase EC-4.1.1.47 BG12063See Table 1 for more details

2-hydroxy-3-oxopropionate reductase (NAD) EC-1.1.1.60 BG13328See Table 1 for more details

D-malate dehydrogenase (NAD) EC-1.1.1.83 BG11222See Table 1 for more details

Cell wall (1) glucosamine-1-phosphate N-acetyltransferase EC-2.3.1.157 BG10113Nucleotides and nucleic acids (3) adenylate kinase (Inorganic triphosphate) EC-2.7.4.3 BG10446

Allantoate aminohydrolase, reversible EC-3.5.3.45-Methylcytosine aminohydrolase EC-3.5.4.1 BG10082

Phosphate and sulfur (2) alkaline phosphatase EC-3.1.3.1 BG10697, BG10183Trimetaphosphate hydrolase EC-3.6.1.2

Transport (49) 2-(hydroxymethyl)phenol transport in/out via proton symport

2-Phosphoglycolate transport in/out via proton symportD-Glycerate 2-phosphate transport in/out via proton symport3'-AMP transport in/out via proton symport3'-CMP transport in via proton symportGuanosine 3'-phsophate transport in/out via proton symport3-Phospho-D-glycerate transport in/out via proton symport3'-UMP transport in via proton symport6-Phospho-D-gluconate transport in/out via proton symportL-arabinitol transport via passive diffusionacetoacetate transport via proton symportN-acetyl-D-mannosamine proton symportN-acetylneuraminate proton symportAMP transport in/out via proton symportD-arabinose reversible transportL-arginine phosphate transport in/out via proton symportL-Citrulline transport in via proton symportCMP transport in/out via proton symportDextrin transport in via proton symportDihydroxyacetone transport via facilitated diffusiondTMP transport in/out via proton symportFructose-6-phosphate transport via phosphate antiportGlucose-1-phosphate transport via phosphate antiportGlucose-6-phosphate transport via phosphate antiportGalactitol transport via PEP:Pyr PTSD-glucosamine 6-phosphate reversible uniportD-glutamate transport in via proton symportglyoxylate transport in via proton symportGlycogen transport inglycine transport in/out via proton symport TC-2.A.3.1GMP transport in/out via proton symporthydroquinone transport in/out via proton symportD-malate transport in via proton symportMAN1P transport in/out via proton symport

MAN6P transport in/out via proton symportmelibiose transport in via symportL-methionine transport out via proton antiportPalatinose transport in via proton symportPhosphoenolpyruvate transport in via proton symportpropionate transport in/out via proton symport TC-2.A.20D-O-Phosphoserine transport in/out via proton symportO-Phospho-L-serine transport in via proton symportRaffinose transport in via proton symportL-rhamnose transport via proton symportD-serine transport in/out via proton symport TC-2.A.3.1L-sorbose reversible transportthymine transport in/out via proton symportTMP transport in/out via proton symportUMP transport in via proton symport

Table S3. List of the reactions identified by in silico analyses based on large-scale gene essentiality data.

1) See supplementary Bacillus subtilis model excel file for detailed equations.

Subsystem Reaction name 1) Protein Classification Locus name CommentTransport (4) chorismate transport in/out via proton symport

Nicotinic acid uptakeL-phenylalanine transport in/out via proton symport TC-2.A.3.1L-tyrosine transport in/out via proton symport TC-2.A.3.1

Lipids (1) 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate reductase (dmpp) BG11662 Only reaction was added

Table S4. Impact of gene deletions on growth in B. subtilis: a complete list of the genes analyzed and predictions**The single-gene deletions were simulated on rich medium (see supplementary Complex medium composition word file) under aerobic conditions, where the reaction corresponding to the deleted gene was removed. 1) Gene names are based on the SubtiList database (http://genolist.pasteur.fr/SubtiList). 2) The in silico results were compared with large-scale experimental gene essentiality data as supplied by

the Bacillus subtilis genome database (http://bacillus.genome.jp). Results are scored as + or meaning growth or no growth determined from in silico/ in vivo data. False-negative (in vivo, growth; in silico, no growth) and false-positive (in vivo, no growth; in silico growth) predictions were detailed in supplementary Table S5 and Table S6, respectively.

Functional classification ID Gene 1)(In vivo/

in silico) 2) CommentAmino acids and related molecules BG10783 asd (-/-)

BG10785 dapA (-/-)BG10944 glyA (-/-)BG10948 glmS (-/-)BG10950 alr (-/-)BG11207 dapB (-/-)BG13301 ykuQ (-/-)BG13302 ykuR (-/-)BG14048 dapF (-/-)BG11964 racE (-/+)BG11840 metK (-+)BG10091 yaaO (+/+)BG10136 cysK (+/+)BG10155 cysE (+/+)BG10195 carA (+/+)BG10196 carB (+/+)BG10212 speA (+/+)BG10284 aroF (+/+)BG10285 aroB (+/+)BG10286 aroH (+/+)BG10287 trpE (+/+)BG10288 trpD (+/+)BG10289 trpF (+/+)BG10290 trpB (+/+)BG10291 trpA (+/+)BG10292 hisC (+/+)BG10293 tyrA (+/+)BG10294 aroE (+/+)BG10300 ansA (+/+)BG10301 ansB (+/+)BG10340 hemA (+/+)BG10350 lysC (+/+)BG10375 aroA (+/+)BG10425 glnA (+/+)BG10457 aroK (+/+)BG10460 hom (+/+)BG10461 thrC (+/+)BG10468 ald (+/+)BG10471 alsS (+/+)BG10509 serA (+/+)BG10538 aroC (+/+)BG10546 ywaA (+/+)BG10621 rocG (+/+)BG10629 ywfE (+/+)BG10667 hutH (+/+)BG10668 hutU (+/+)

BG10670 ilvB (+/+)BG10672 ilvC (+/+)BG10673 ilvA (+/+)BG10675 leuB (+/+)BG10715 pyrAA (+/+)BG10716 pyrAB (+/+)BG10722 rocD (+/+)BG10736 rsbX (+/+)BG10784 dapG (+/+)BG10811 gltA (+/+)BG10841 proG (+/+)BG10842 dppA (+/+)BG10932 rocF (+/+)BG10963 proB (+/+)BG10964 proA (+/+)BG11038 trpC (+/+)BG11049 proH (+/+)BG11096 nasD (+/+)BG11097 nasE (+/+)BG11099 hutG (+/+)BG11100 hutI (+/+)BG11116 asnH (+/+)BG11117 mmsA (+/+)BG11435 gudB (+/+)BG11522 aroD (+/+)BG11532 ilvD (+/+)BG11627 msrA (+/+)BG11628 yppQ (+/+)BG11723 bcd (+/+)BG11744 proI (+/+)BG11747 dsdA (+/+)BG11831 asnB (+/+)BG11838 ggt (+/+)BG11930 cysH (+/+)BG11948 leuA (+/+)BG11949 leuC (+/+)BG11950 leuD (+/+)BG11981 ureA (+/+)BG11982 ureB (+/+)BG11983 ureC (+/+)BG12011 ycgM (+/+)BG12033 yclM (+/+)BG12043 gabT (+/+)BG12044 gabD (+/+)BG12240 asnO (+/+)BG12290 yrhA (+/+)BG12291 yrhB (+/+)BG12306 yrpC (+/+)BG12362 alaT (+/+)BG12460 speE (+/+)BG12461 speB (+/+)BG12597 hisA (+/+)BG12601 hisG (+/+)BG12602 hisH (+/+)BG12610 kbl (+/+)BG12658 proJ (+/+)BG12673 serC (+/+)

BG12685 tdh (+/+)BG12749 ybgE (+/+)BG12753 ybgJ (+/+)BG12914 yfjR (+/+)BG13147 goxB (+/+)BG13162 yjcI (+/+)BG13163 yjcJ (+/+)BG13278 ykrS (+/+)BG13279 ykrT (+/+)BG13281 ykrV (+/+)BG13282 ykrW (+/+)BG13283 ykrX (+/+)BG13284 ykrY (+/+)BG13285 ykrZ (+/+)BG13350 ylaM (+/+)BG13371 ylmB (+/+)BG13379 cysC (+/+)BG13397 sdaAB (+/+)BG13398 sdaAA (+/+)BG13542 kamA (+/+)BG13800 mtn (+/+)BG13832 speD (+/+)BG10906 bltD (+/+)BG11933 def (+/+)BG13931 hisJ (+/+)BG10191 argC No experimental dataBG10192 argJ No experimental dataBG10193 argB No experimental dataBG10194 argD No experimental dataBG10197 argF No experimental dataBG10205 patA No experimental dataBG10462 thrB No experimental dataBG10510 lysA No experimental dataBG10622 rocA No experimental dataBG10671 ilvH No experimental dataBG10913 pheB No experimental dataBG10914 pheA No experimental dataBG11513 aspB No experimental dataBG11534 metA No experimental dataBG12569 yodQ No experimental dataBG12570 argG No experimental dataBG12571 argH No experimental dataBG12594 gltB No experimental dataBG12598 hisB No experimental dataBG12599 hisD No experimental dataBG12600 hisF No experimental dataBG12603 hisI No experimental dataBG12616 metE No experimental dataBG12627 mtbP No experimental data

Carbohydrates and related molecule BG10109 ispE (-/-)BG10403 yvyH (-/-)BG11366 gpsA (-/-)BG11715 dxs (-/-)BG12704 ybbT (-/-)BG13409 dxr (-/-)BG10207 pdhA (-/+)BG10273 odhB (-/+)

BG10412 fbaA (-/+)BG10897 tpiA (-/+)BG11062 pgk (-/+)BG11247 tkt (-/+)BG12644 pfkA (-/+)BG13328 ykwC (+/+)BG10043 maa (+/+)BG10177 gutB (+/+)BG10187 glpK (+/+)BG10188 glpD (+/+)BG10189 yhxB (+/+)BG10208 pdhB (+/+)BG10209 pdhC (+/+)BG10210 pdhD (+/+)BG10272 odhA (+/+)BG10351 sdhC (+/+)BG10352 sdhA (+/+)BG10353 sdhB (+/+)BG10367 acuC (+/+)BG10368 acuB (+/+)BG10369 acuA (+/+)BG10370 acsA (+/+)BG10384 citG (+/+)BG10413 ywjH (+/+)BG10454 pmi (+/+)BG10472 alsD (+/+)BG10473 amyE (+/+)BG10478 citB (+/+)BG10545 gdh (+/+)BG10581 galK (+/+)BG10582 galT (+/+)BG10596 sacA (+/+)BG10634 pta (+/+)BG10649 gntK (+/+)BG10669 idh (+/+)BG10806 xylA (+/+)BG10807 xylB (+/+)BG10813 ackA (+/+)BG10827 gapA (+/+)BG10854 citA (+/+)BG10855 citZ (+/+)BG10856 icd (+/+)BG10907 glgB (+/+)BG10908 glgC (+/+)BG10909 glgD (+/+)BG10910 glgA (+/+)BG10911 glgP (+/+)BG10926 pksG (+/+)BG10935 bglH (+/+)BG10942 ywlF (+/+)BG11010 treA (+/+)BG11103 yxaA (+/+)BG11109 yxaG (+/+)BG11118 iolB (+/+)BG11119 iolC (+/+)BG11120 iolD (+/+)BG11121 iolE (+/+)

BG11125 fbaB (+/+)BG11153 scoA (+/+)BG11154 scoB (+/+)BG11158 ycbC (+/+)BG11161 ycbF (+/+)BG11163 ycbH (+/+)BG11198 phy (+/+)BG11203 bglA (+/+)BG11211 mgsA (+/+)BG11216 mtlD (+/+)BG11222 ycsA (+/+)BG11322 mmgD (+/+)BG11323 mmgE (+/+)BG11355 aldX (+/+)BG11363 iolS (+/+)BG11386 mdh (+/+)BG11396 kdgA (+/+)BG11397 kdgK (+/+)BG11400 kduD (+/+)BG11401 kduI (+/+)BG11478 fbp (+/+)BG11601 yhcW (+/+)BG11685 glcK (+/+)BG11720 yqiQ (+/+)BG11722 ptb (+/+)BG11724 buk (+/+)BG11733 yqjD (+/+)BG11738 yqjI (+/+)BG11739 zwf (+/+)BG11762 nudF (+/+)BG11818 yktC (+/+)BG11837 galE (+/+)BG11839 malA (+/+)BG11841 pckA (+/+)BG11900 abfA (+/+)BG11902 adhB (+/+)BG11903 aldY (+/+)BG11904 araA (+/+)BG11905 araB (+/+)BG11906 araD (+/+)BG12063 ydaP (+/+)BG12195 ydhR (+/+)BG12320 ysfC (+/+)BG12366 pgi (+/+)BG12385 yulC (+/+)BG12387 yulE (+/+)BG12420 yvdK (+/+)BG12421 malL (+/+)BG12422 pgcM (+/+)BG12439 lacA (+/+)BG12558 acoA (+/+)BG12559 acoB (+/+)BG12560 acoC (+/+)BG12561 acoL (+/+)BG12562 adhA (+/+)BG12582 dhaS (+/+)BG12588 fruK (+/+)

BG12592 gapB (+/+)BG12615 melA (+/+)BG12630 nagA (+/+)BG12631 nagB (+/+)BG12657 pps (+/+)BG12660 pycA (+/+)BG12661 pyk (+/+)BG12746 gamA (+/+)BG12796 ydjE (+/+)BG12803 ydjL (+/+)BG13020 yhdN (+/+)BG13177 manA (+/+)BG13204 uxaC (+/+)BG13207 yjmD (+/+)BG13208 uxuA (+/+)BG13212 uxaB (+/+)BG13213 uxaA (+/+)BG13393 rpe (+/+)BG13456 yngE (+/+)BG13484 yoaN (+/+)BG13826 ytbE (+/+)BG13829 ytcB (+/+)BG13922 ytsJ (+/+)BG14096 yvgN (+/+)BG14148 oxdC (+/+)BG10898 pgmBG10899 enoBG10877 rbsK No experimental dataBG11350 licH No experimental dataBG11985 xsa No experimental dataBG12680 sucC No experimental dataBG12681 sucD No experimental data

Cell wall BG10113 gcaD (-/-)BG10225 murD (-/-)BG10227 murG (-/-)BG10228 murB (-/-)BG10449 tagD (-/-)BG10450 tagA (-/-)BG10451 tagB (-/-)BG10725 tagF (-/-)BG10973 murC (-/-)BG11191 tagH (-/-)BG11205 tagG (-/-)BG11932 ddl (-/-)BG12084 murF (-/-)BG12684 tagO (-/-)BG11955 murAA (-/+)BG10402 gtaB (+/-)BG10548 dltD (+/-)BG10549 dltC (+/-)BG10550 dltB (+/-)BG10551 dltA (+/-)BG10724 tagE (+/-)BG11192 ggaB (+/-)BG11367 ggaA (+/-)BG13951 yubB (+/-)BG10407 lytC (+/+)

BG10414 murAB (+/+)BG10455 lytD (+/+)BG10825 cwlC (+/+)BG11514 cwlD (+/+)BG11633 cwlH (+/+)BG12688 tuaA (+/+)BG12689 tuaB (+/+)BG12690 tuaC (+/+)BG12691 tuaD (+/+)BG12692 tuaE (+/+)BG12694 tuaG (+/+)BG12695 tuaH (+/+)BG10223 murE No experimental dataBG10224 mraY No experimental dataBG10505 cwlA No experimental data

Coenzymes and prosthetic group BG13824 ytaG (-/+)BG13966 yueK (-/+)BG11638 yqeJ (-/-)BG10279 hepS (-/-)BG10280 menH (-/-)BG10281 hepT (-/-)BG10552 menA (-/-)BG10683 menD (-/-)BG10686 menB (-/-)BG10687 menE (-/-)BG10694 nadE (-/-)BG10795 dfrA (-/-)BG11711 folD (-/-)BG13847 menC (-/-)BG11098 nasF (+/+)BG11789 amhX (+/+)BG13115 yitJ (+/+)BG13237 ykkE (+/+)BG13313 ykvK (+/+)BG13361 ylbI (+/+)BG13369 ylbQ (+/+)BG13380 ylnD (+/+)BG13381 ylnE (+/+)BG13382 ylnF (+/+)BG13388 yloI (+/+)BG13965 yueJ (+/+)BG10075 yaaD (+/+)BG10076 yaaE (+/+)BG10137 pabB (+/+)BG10138 pabA (+/+)BG10139 pabC (+/+)BG10140 sul (+/+)BG10141 folB (+/+)BG10142 folK (+/+)BG10277 mtrA (+/+)BG10322 folC (+/+)BG10342 hemC (+/+)BG10343 hemD (+/+)BG10344 hemB (+/+)BG10345 hemL (+/+)BG10429 hemE (+/+)BG10430 hemH (+/+)

BG10431 hemY (+/+)BG10518 ribD (+/+)BG10682 menF (+/+)BG10693 thiL (+/+)BG10791 tenA (+/+)BG10867 nadB (+/+)BG10868 nadC (+/+)BG11019 dhbA (+/+)BG11020 dhbE (+/+)BG11241 dhbB (+/+)BG11242 dhbC (+/+)BG11246 thiC (+/+)BG11395 hemN (+/+)BG11495 ribC (+/+)BG11519 panB (+/+)BG11524 bioA (+/+)BG11525 bioB (+/+)BG11527 bioF (+/+)BG11529 bioW (+/+)BG11748 coaA (+/+)BG11943 gsaB (+/+)BG11969 ribR (+/+)BG12629 nadA (+/+)BG12999 hemZ (+/+)BG13151 yjbV (+/+)BG10519 ribE No dataBG10520 ribA No dataBG10521 ribH No dataBG10571 thiM No dataBG10572 thiE No dataBG10598 thiD No dataBG11493 panD No dataBG11520 panC No dataBG11526 bioD No data

Lipids BG13926 accD (-/-)BG10152 yacM (-/-)BG10153 yacN (-/-)BG11206 birA (-/-)BG11373 pgsA (-/-)BG11383 accB (-/-)BG11384 accC (-/-)BG11535 fabG (-/-)BG11662 yqfP (-/-)BG11671 yqfY (-/-)BG11714 yqiD (-/-)BG11836 fabD (-/-)BG12557 accA (-/-)BG12575 cdsA (-/-)BG13021 yhdO (-/-)BG13128 fabF (-/-)BG12089 acpS (-/+)BG10305 bkdB (+/-)BG10306 bkdAB (+/-)BG10307 bkdAA (+/-)BG11725 lpdV (+/-)BG11012 pssA (+/-)BG11013 psd (+/-)

BG11611 ugtP (+/-)BG12900 yfiX (+/-)BG11040 dgkA (+/+)BG10646 glpQ (+/+)BG11225 ycsD (+/+)BG11239 acdA (+/+)BG11305 ywiE (+/+)BG11310 ywjE (+/+)BG11319 mmgA (+/+)BG11320 mmgB (+/+)BG11321 mmgC (+/+)BG11440 ypgA (+/+)BG11946 lcfA (+/+)BG12080 ydbM (+/+)BG12221 fabL (+/+)BG12331 ysiB (+/+)BG12483 ywnE (+/+)BG12496 ywpB (+/+)BG13048 fabHB (+/+)BG13057 yhfL (+/+)BG13064 yhfT (+/+)BG13127 fabHA (+/+)BG13152 fabI (+/+)BG13408 uppS (+/+)BG13457 yngF (+/+)BG13458 yngG (+/+)BG13460 yngI (+/+)BG13461 yngJ (+/+)BG13523 yocJ (+/+)BG14022 yusJ (+/+)BG14023 yusK (+/+)BG14024 yusL (+/+)

Membrane bioenergetics BG12391 yumC (-/+)BG12398 trxB (-/+)BG10213 ctaA (+/+)BG10214 ctaB (+/+)BG10215 ctaC (+/+)BG10216 ctaD (+/+)BG10217 ctaE (+/+)BG10218 ctaF (+/+)BG10583 qoxA (+/+)BG10584 qoxB (+/+)BG10585 qoxC (+/+)BG10586 qoxD (+/+)BG10589 nfrA (+/+)BG10817 atpF (+/+)BG10818 atpH (+/+)BG10819 atpA (+/+)BG10820 atpG (+/+)BG10821 atpD (+/+)BG10822 atpC (+/+)BG10979 fdhD (+/+)BG11081 narG (+/+)BG11082 narH (+/+)BG11083 narJ (+/+)BG11094 nasB (+/+)BG11095 nasC (+/+)

BG11325 qcrA (+/+)BG11326 qcrB (+/+)BG11327 qcrC (+/+)BG11925 cydA (+/+)BG11926 cydB (+/+)BG12018 ycgT (+/+)BG12040 ycnD (+/+)BG12294 yrhE (+/+)BG12390 yumB (+/+)BG12931 yfkO (+/+)BG13183 ctaO (+/+)BG13190 yjgC (+/+)BG13203 yjlD (+/+)BG13476 yoaE (+/+)BG13857 ythA (+/+)BG13858 ythB (+/+)BG14046 yutJ (+/+)BG19003 ldh (+/+)BG10814 atpI No experimental dataBG10815 atpB No experimental dataBG10816 atpE No experimental data

Nucleotides and nucleic acids BG10092 tmk (-/-)BG10114 prs (-/-)BG10446 adk (-/-)BG13143 yjbN (-/-)BG13386 gmk (-/-)BG10073 guaB (-/+)BG10131 hprT (-/+)BG10410 pyrG (-/+)BG11004 cmk (-/+)BG11404 nrdE (-/+)BG11405 nrdF (-/+)BG11426 ymaA (-/+)BG10282 ndk (+/-)BG10002 purA (+/+)BG10078 dck (+/+)BG10079 dgk (+/+)BG10082 yaaJ (+/+)BG10419 tdk (+/+)BG10477 cdd (+/+)BG10481 comEB (+/+)BG10647 guaA (+/+)BG10700 purE (+/+)BG10701 purK (+/+)BG10702 purB (+/+)BG10703 purC (+/+)BG10704 purS (+/+)BG10705 purL (+/+)BG10706 purQ (+/+)BG10707 purF (+/+)BG10708 purM (+/+)BG10709 purN (+/+)BG10710 purH (+/+)BG10711 purD (+/+)BG10713 pyrB (+/+)BG10714 pyrC (+/+)BG10717 pyrK (+/+)

BG10718 pyrD (+/+)BG10719 pyrF (+/+)BG10720 pyrE (+/+)BG10794 thyB (+/+)BG10924 purT (+/+)BG10945 upp (+/+)BG10983 dra (+/+)BG10985 pdp (+/+)BG11044 adeC (+/+)BG11079 xpt (+/+)BG11190 thyA (+/+)BG11330 punA (+/+)BG11331 drm (+/+)BG12392 guaC (+/+)BG12568 apt (+/+)BG12581 deoD (+/+)BG12665 relA (+/+)BG12675 pyrH (+/+)BG12696 udk (+/+)BG12930 yfkN (+/+)BG13240 guaD (+/+)BG13437 yncF (+/+)BG13982 pucH (+/+)BG13986 pucL (+/+)BG13987 pucM (+/+)BG13988 pucE (+/+)BG13989 pucD (+/+)BG13990 pucC (+/+)BG13991 pucB (+/+)BG13992 pucA (+/+)BG13728 yosS No experimental data

Other function BG11937 fmt (-/+)BG10849 katA (+/+)BG11102 katE (+/+)BG11940 gbsA (+/+)BG11941 gbsB (+/+)BG11945 katX (+/+)BG10781 spoVFA (+/+)BG10782 spoVFB (+/+)BG11016 penP (+/+)BG11507 ybxI (+/+)BG11530 bsaA (+/+)BG11676 sodA (+/+)BG11885 yxeI (+/+)BG10101 metS No experimental dataBG10154 gltX No experimental data

Phosphate and sulfur BG10014 ppaC (-/-)BG10183 phoA (+/+)BG10658 ssuD (+/+)BG10697 phoB (+/+)BG14099 yvgQ (+/+)BG14100 yvgR (+/+)BG13378 sat (+/+)

Transport BG12344 mrpF (-/+)BG12345 mrpD (-/+)BG12355 mrpA (-/+)BG12356 mrpB (-/+)

BG12357 mrpC (-/+)BG10186 glpF (+/+)BG10198 ptsG (+/+)BG10200 ptsH (+/+)BG10201 ptsI (+/+)BG10316 levD (+/+)BG10317 levE (+/+)BG10318 levF (+/+)BG10319 levG (+/+)BG10562 ywbA (+/+)BG10573 ywbL (+/+)BG10574 ywbM (+/+)BG10575 ywbN (+/+)BG10577 ywcA (+/+)BG10594 ywcJ (+/+)BG10595 sacP (+/+)BG10645 glpT (+/+)BG10650 gntP (+/+)BG10656 ssuA (+/+)BG10657 ssuC (+/+)BG10835 feuA (+/+)BG10836 feuB (+/+)BG10837 feuC (+/+)BG10843 dppB (+/+)BG10844 dppC (+/+)BG10845 dppD (+/+)BG10846 dppE (+/+)BG10869 nrgA (+/+)BG10905 blt (+/+)BG10933 rocE (+/+)BG10934 bglP (+/+)BG10984 nupC (+/+)BG10991 ykqB (+/+)BG10992 pyrP (+/+)BG11009 treP (+/+)BG11014 gamP (+/+)BG11075 yqxL (+/+)BG11080 pbuX (+/+)BG11093 nasA (+/+)BG11101 hutM (+/+)BG11122 iolF (+/+)BG11146 citH (+/+)BG11150 yxjA (+/+)BG11160 ycbE (+/+)BG11185 yckI (+/+)BG11186 yckJ (+/+)BG11187 yckK (+/+)BG11215 mtlA (+/+)BG11328 gabP (+/+)BG11338 natA (+/+)BG11339 natB (+/+)BG11342 narK (+/+)BG11348 licC (+/+)BG11371 opuAB (+/+)BG11372 opuAC (+/+)BG11375 pstS (+/+)BG11376 pstC (+/+)

BG11377 pstA (+/+)BG11378 pstBA (+/+)BG11379 pstBB (+/+)BG11399 kdgT (+/+)BG11562 ybaR (+/+)BG11567 ybbF (+/+)BG11590 yhcL (+/+)BG11647 yqeW (+/+)BG11727 yqiX (+/+)BG11728 yqiY (+/+)BG11729 yqiZ (+/+)BG11763 mleN (+/+)BG11798 alsT (+/+)BG11832 citM (+/+)BG11848 malP (+/+)BG11875 yvfH (+/+)BG11878 yxeB (+/+)BG11894 yxeR (+/+)BG11907 araE (+/+)BG11910 araN (+/+)BG11911 araP (+/+)BG11912 araQ (+/+)BG11915 azlC (+/+)BG11916 azlD (+/+)BG11918 brnQ (+/+)BG11931 czcD (+/+)BG11938 fruA (+/+)BG11958 opuD (+/+)BG11980 trkA (+/+)BG12001 lctP (+/+)BG12002 mdr (+/+)BG12013 ycgO (+/+)BG12034 yclN (+/+)BG12035 yclO (+/+)BG12036 yclP (+/+)BG12037 yclQ (+/+)BG12046 ycnJ (+/+)BG12065 mntH (+/+)BG12075 dctP (+/+)BG12148 ydfA (+/+)BG12190 ydhM (+/+)BG12191 ydhN (+/+)BG12192 ydhO (+/+)BG12232 ssuB (+/+)BG12279 yraO (+/+)BG12296 yrhG (+/+)BG12343 mrpG (+/+)BG12353 maeN (+/+)BG12369 yugO (+/+)BG12411 yvdB (+/+)BG12416 yvdG (+/+)BG12417 yvdH (+/+)BG12418 yvdI (+/+)BG12436 yvfK (+/+)BG12437 yvfL (+/+)BG12438 yvfM (+/+)BG12492 ywoE (+/+)

BG12520 ywrA (+/+)BG12521 ywrB (+/+)BG12527 ywrK (+/+)BG12546 yxkJ (+/+)BG12548 yxlA (+/+)BG12564 amyC (+/+)BG12573 braB (+/+)BG12625 msmE (+/+)BG12641 opuE (+/+)BG12750 ybgF (+/+)BG12752 ybgH (+/+)BG12763 ycdH (+/+)BG12764 ycdI (+/+)BG12765 yceA (+/+)BG12795 gutP (+/+)BG12802 ydjK (+/+)BG12811 pbuG (+/+)BG12849 yesO (+/+)BG12850 yesP (+/+)BG12851 yesQ (+/+)BG12876 yfhA (+/+)BG12901 yfiY (+/+)BG12902 yfiZ (+/+)BG12913 yfjQ (+/+)BG12922 yfkE (+/+)BG12941 nagP (+/+)BG12951 yflS (+/+)BG12954 yfmC (+/+)BG12955 yfmD (+/+)BG12956 yfmE (+/+)BG12957 yfmF (+/+)BG12983 yhaG (+/+)BG12997 yhaU (+/+)BG13044 nhaC (+/+)BG13075 glcP (+/+)BG13100 yisU (+/+)BG13146 yjbQ (+/+)BG13176 manP (+/+)BG13210 exuT (+/+)BG13226 pit (+/+)BG13256 ykoK (+/+)BG13275 ykrM (+/+)BG13325 ykvW (+/+)BG13377 cysP (+/+)BG13384 yloB (+/+)BG13473 yoaB (+/+)BG13529 yocS (+/+)BG13535 yodF (+/+)BG13554 yojA (+/+)BG13784 yrbD (+/+)BG13851 mntA (+/+)BG13852 mntB (+/+)BG13853 mntC (+/+)BG13854 mntD (+/+)BG13864 ytiP (+/+)BG13884 ytmJ (+/+)BG13885 ytmK (+/+)

BG13886 ytmL (+/+)BG13887 ytmM (+/+)BG13891 ytnA (+/+)BG13912 ytrB (+/+)BG13913 ytrC (+/+)BG13914 ytrD (+/+)BG13915 ytrE (+/+)BG13916 ytrF (+/+)BG13943 yuaA (+/+)BG13956 yubG (+/+)BG13984 pucJ (+/+)BG13985 pucK (+/+)BG14013 yusA (+/+)BG14014 yusB (+/+)BG14015 yusC (+/+)BG14047 yutK (+/+)BG14093 yvgK (+/+)BG14094 yvgL (+/+)BG14095 yvgM (+/+)BG14098 yvgP (+/+)BG14105 yvgW (+/+)BG14106 yvgX (+/+)BG14107 yvgY (+/+)BG14141 yvrA (+/+)BG14142 yvrB (+/+)BG14143 yvrC (+/+)BG14154 yvsH (+/+)BG14181 mrpE (+/+)BG10624 rocC No experimental dataBG10828 fhuD No experimental dataBG10878 rbsD No experimental dataBG10879 rbsA No experimental dataBG10880 rbsC No experimental dataBG10881 rbsB No experimental dataBG11015 gltP No experimental dataBG11303 arsB No experimental dataBG11347 licB No experimental dataBG11349 licA No experimental dataBG11370 opuAA No experimental dataBG11389 fhuB No experimental dataBG11390 fhuC No experimental dataBG11391 fhuG No experimental dataBG11485 glnQ No experimental dataBG11486 glnH No experimental dataBG11487 glnM No experimental dataBG11488 glnP No experimental dataBG12565 amyD No experimental dataBG12595 gltT No experimental dataBG12604 ytmN No experimental dataBG12633 opuBA No experimental dataBG12634 opuBB No experimental dataBG12635 opuBC No experimental dataBG12636 opuBD No experimental dataBG12637 opuCA No experimental dataBG12638 opuCB No experimental dataBG12639 opuCC No experimental dataBG12640 opuCD No experimental data

SI Table 5. False-negative in silico growth predictions compared with large-scale gene essentiality (Kobayashi et al., 2003). In vivo shows growth but in silico shows no growth.Functional classification

Gene1) Product or function EC number Comment Reference

Nucleotides and nucleic acids

ndk Nucleoside diphosphate kinase 2.7.4.6 Metabolic gap and/or external source 2)

Kobayashi et al., 2003

Lipids bkdAA Branched-chain alpha-keto acid dehydrogenase E1 subunit

Metabolic gap and/or external source 3)

Kobayashi et al., 2003; Willecke and Pardee, 1971

bkdAB Branched-chain alpha-keto acid dehydrogenase E1 subunit

bkdB Branched-chain alpha-keto acid dehydrogenase E2 subunit

ipdV Branched-chain alpha-keto acid dehydrogenase E3 subunit

pssA Phosphatidylserine synthase 2.7.8.8 Biomass composition 4) Matsumoto et al., 1998psd Phosphatidylserine decarboxylase 4.1.1.65 Biomass composition 4) Matsumoto et al., 1998yfiX Lysylphosphatidylglycerol synthesis Biomass composition 4) Kobayashi et al., 2003

Nishibori et al., 2005ugtP UDP-glucosyltransferase Biomass composition 4) Kobayashi et al., 2003

Nishibori et al., 2005Cell wall gtaB UTP-glucose-1-phosphate uridylyltransferase 2.7.7.9 Biomass composition 4)

dltA D-Alanyl-D-alanine carrier protein ligase Biomass composition 4) Perego et al., 1995; Wecke et al., 1996;

dltB D-Alanine transfer from D-alanine carrier protein to undecaprenol-phosphate

Biomass composition 4) Perego et al., 1995; Wecke et al., 1996;

dltC D-Alanine carrier protein Biomass composition 4) Perego et al., 1995; Wecke et al., 1996;

dltD D-Alanine transfer from undecaprenol-phosphate to the poly(glycerophosphate) chain

Biomass composition 4) Perego et al., 1995; Wecke et al., 1996;

ggaA Galactosamine-containing minor teichoic acid biosynthesis protein

Biomass composition 4)

ggaB Galactosamine-containing minor teichoic acid biosynthesis protein

Biomass composition 4)

tagE UDP-glucose:polyglycerol phosphate glucosyltransferase

2.4.1.52 Biomass composition 4)

yubB Undecaprenyl-diphosphatase 3.6.1.27 Metabolic gap and/or

external source 5)

1) Gene names are based on the SubtiList database (http://genolist.pasteur.fr/SubtiList/).2) In the metabolic model, dTTP and dCTP necessary for DNA synthesis can only produced by ndk gene product. 3) B. subtilis mutant lacking the activity of branched strain alpha-keto acid dehydrogenase can grow on in the presence of isovalerate, isobutyrate or 2- methylbutyrate (Willecke and

Pardee, 1971), but relevant metabolic pathways utilizing these acids have not been identified. Isovaleryl-, 2-methylbutyryl- or isobutyryl-CoA necessary for branched long-chain fatty acids synthesis might be generated from external source and/or by unknown pathways.

4) These metabolic genes are related to generation of lipids and cell wall components not essential for cell growth. In this study, biomass synthesis equation developed based on cellular composition of wild-type B. subtilis, was used as an objective function of flux balance analysis.

5) Related to peptidoglycan subunit synthesis. Reaction product, undecaprenyl phosphate, might be generated from external source and/or by unknown pathway(s).

Reference

Kobayashi K, Ehrlich SD, Albertini A, Amati G, Andersen KK, Arnaud M, Asai K, Ashikaga S, Aymerich S, Bessieres P et al. (2003) Essential Bacillus subtilis genes. Proc Natl Acad

Sci USA 100:4 678-83.

Matsumoto K, Okada M, Horikoshi Y, Matsuzaki H, Kishi T, Itaya M, Shibuya I (1998) Cloning, sequencing, and disruption of the Bacillus subtilis psd gene coding for

phosphatidylserine decarboxylase. J Bacteriol 180: 100-6.

Nishibori A, Kusaka J, Hara H, Umeda M, Matsumoto K (2005) Phosphatidylethanolamine domains and localization of phospholipid synthases in Bacillus subtilis membranes. J

Bacteriol 187: 2163-74.

Perego M, Glaser P, Minutello A, Strauch MA, Leopold K, Fischer W (1995) Incorporation of D-alanine into lipoteichoic acid and wall teichoic acid in Bacillus subtilis. Identification

of genes and regulation. J Biol Chem 270: 15598-606.

Wecke J, Perego M, Fischer W (1996) D-alanine deprivation of Bacillus subtilis teichoic acids is without effect on cell growth and morphology but affects the autolytic activity.

Microb Drug Resist 2: 123-9.

Willecke K, Pardee AB (1971) Fatty acid-requiring mutant of bacillus subtilis defective in branched chain alpha-keto acid dehydrogenase. J Biol Chem 246: 5264-72.

Table S6. False-positive in silico growth predictions compared with large-scale experimental gene essentiality data (Kobayashi et al., 2003). In vivo shows no growth, but in silico shows growth.

Functional classification Gene 1) Product or function EC no. Comment 1) ReferenceAmino acids and related molecules

metK S-adenosylmethionine synthetase

2.5.1.6 Synthesize S-adenosylmethionine, which is necessary for siroheme synthesis.

von Wachenfeldt and Hederstedt, 2002

racE glutamate racemase 5.1.1.3 Regulation effect. racE could not be replaced by yrpC.

Kobayashi et al., 2003

Carbohydrates and related molecules

pdhA Pyruvate dehydrogenase E1 alpha subunit

1.2.1.51 Not well understood.

odhB 2-Oxoglutarate dehydrogenase complex E2 subunit

Not well understood.

fbaA Fructose-1,6-bisphosphate aldolase

4.1.2.13 Possibly regulation effect. fbaA could not be replaced by fbaB.

tpiA Triose-phosphate isomerase

5.3.1.1 Possibly toxic effect. Accumulation of dihydroxyacetone phosphate, which may leads to the formation of the bactericidal compound methylglyoxal

Fraenkel, 1996

pgk Phosphoglycerate kinase 2.7.2.3 Conditionally essential gene. Nakano et al., 1999

tkt Transketolase 2.2.1.1 Not well understood.

pfkA Phosphofructokinase 2.7.1.11 Not well understood.

Cell wall murAA UDP-N-acetylglucosamine 1-carboxyvinyltransferase

2.5.1.7 Possibly regulation effect. murAA could not replaced by a homologue murAB.

Coenzymes and prosthetic groups

ytaG Dephospho-CoA kinase 2.7.1.24 Synthesize coenzyme A.

yueK Nicotinate phosphoribosyltransferase

2.4.2.11 Toxic effect. Nicotinate accumulation. Kobayashi et al., 2003

Lipids acpS Acyl-carrier protein synthase

2.7.8.7 Synthesize acyl-carrier protein.

Membrane bioenergetics yumC Thioredoxin reductase (NADPH)

1.8.1.9 Possibly regulation effect. Both yumC and trxB products seem to be essential for cell growth.

Kobayashi et al., 2003

trxB Thioredoxin reductase (NADPH)

1.8.1.9 Possibly regulation effect. Both yumC and trxB products seem to be essential for cell growth.

Kobayashi et al., 2003

Nucleotides and nucleic acids guaB IMP dehydrogenase 1.1.1.205 Not well understood.hprT Guanine

phosphoribosyltransferaseNot well understood.

pyrG CTP synthase 6.3.4.2 Not well understood.cmk cytidylate kinase (dCMP) 2.7.4.14 Not well understood.nrdE Nucleoside-diphosphate

reductase subunit1.17.4.1 Not well understood.

nrdF Nucleoside-diphosphate reductase subunit

1.17.4.1 Not well understood.

ymaA Nucleoside-diphosphate reductase subunit

1.17.4.1 Not well understood.

Other functions fmt Methionyl-tRNA formyltransferase

2.1.2.9 Other function. Required for the formylation of methionyl tRNA

Kobayashi et al., 2003

Transport mrpF Sodium/potassium transporter

Other function. Multiple resistance and pH homeostasis

Kobayashi et al., 2003

mrpD Sodium/potassium transporter

Other function. Multiple resistance and pH homeostasis

Kobayashi et al., 2003

mrpA Sodium/potassium transporter

Other function. Multiple resistance and pH homeostasis

Kobayashi et al., 2003

mrpB Sodium/potassium transporter

Other function. Multiple resistance and pH homeostasis

Kobayashi et al., 2003

mrpC Sodium/potassium transporter

Other function. Multiple resistance and pH homeostasis

Kobayashi et al., 2003

1) Gene names are based on the SubtiList database (http://genolist.pasteur.fr/SubtiList/)..

Reference

Fraenkel DG (1996) Glycolysis. In FC Neidhardt (ed.), Escherichia coli and Salmonella: Cellular and Molecular Biology. American Society of Microbiology, Washington, D.C. Vol.

1, p189-198.

Kobayashi K, Ehrlich SD, Albertini A, Amati G, Andersen KK, Arnaud M, Asai K, Ashikaga S, Aymerich S, Bessieres P et al. (2003) Essential Bacillus subtilis genes. Proc Natl Acad

Sci USA 100:4 678-83.

Nakano MM, Zhu Y, Haga K, Yoshikawa H, Sonenshein AL, Zuber P (1999) A mutation in the 3-phosphoglycerate kinase gene allows anaerobic growth of Bacillus subtilis in the

absence of ResE kinase. J Bacteriol 181: 7087-97.

von Wachenfeldt C, Hederstedt L (2002) Respiratory cytochromes, other heme proteins, and heme biosynthesis. In A. L. Sonenshein, J. A. Hoch, and R. Losick (eds.), Bacillus subtilis

and its closest relatives. From genes to cells. American Society of Microbiology, Washington, D.C. p163-79.

Table S7. Comparison of in silico metabolites and experimental metabolomic data

1) From supporting information Table 1 of Ref: Soga T, Ohashi Y, Ueno Y, Naraoka H, Tomita M,

Nishioka (2003) Quantitative metabolome analysis using capillary electrophoresis mass spectrometry. J

Proteome Research 2: 488-94) 2) From KEGG database (http://www.genome.jp).3) See supplementary Bacillus subtilis model excel file.

No. Compounds 1) KEGG no. 2) CAS no.In silico

metabolite 3)

1 Urea C00086 57-13-6 O2 3-Aminopropionitrile C05670 151-18-8

3 Methylguanidine C02294 

4 1,3-Diaminopropane C00986 109-76-25 L-Gly C00037 56-40-6 O6 Isopropanolamine7 Thioacetate C01857 507-09-58 Cysteamine C01678 60-23-1 O9 Pyridine C00747 110-86-1

10 Pyrimidine C00396 289-95-2

11 3-Amino-1,2,4-triazole C11261 

12 Piperidine C1016513 Piperazine14 1,4-Butanediamine C00134 110-60-1 O15 L-beta-Ala C00099 107-95-9 O16 L-Ala C00041 56-41-7 O17 Sarcosine C00213 107-97-1 O18 3-Amino-1,2-propanediol

19 2-Hydroxypyridine C02502  20 Aniline C00292 62-53-321 4-Hydroxymethyl imidazole22 1-Methyl-2-pyrrolidone

23 Succinimide C07273 24 alpha-Aminocyclopropane-1-carboxylate C01234 22059-21-8

25 Hexylamine C0830626 Cadaverine (1,5-Diaminopentane) C01672 462-94-2 O27 alpha-Aminoisobutyrate28 GABA C00334 56-12-2 O

29 N,N-Dimethylglycine C01026

30 N-Methyl-DL-alanine C02721 

31 DL-2,3-Diaminopropionate C03401 32 L-Ser C00065 56-45-1 O

33 Diethanolamine C06772 

34 Phenyl hydrazine C02304 35 Hypotaurine C00519 300-84-5

36 4-Aminophenol C02372  37 Cytosine C00380 71-30-7 O38 Uracil C00106 66-22-8 O39 Creatinine C00791 60-27-540 Dihydrouracil C00429 504-07-441 1-Methylhydantoin C02565 616-04-642 L-Pro C00148 147-85-3 O

43 L-Val C00183 72-18-4 O

44 L-Norvaline C01826 45 Guanidinoacetate C00581 352-97-6

46 Benzimidazole C02009 47 L-Homoserine C00263 672-15-1 O48 L-Thr C00188 72-19-5 O49 alpha-Methyl-DL-serine

50 Benzamidine C01784 51 Purine C00465 120-73-0 O52 L-Cys C00097 52-90-4 O

53 N,N-Dimethylaniline C02846  

54 Benzamide C09815 

55 beta-Phenylethylamine C0533256 Taurine C00245 107-35-7 O57 1-Methylhistamine C05127 673-50-758 5-Methyl cytosine C02376 554-01-8 O59 Imidazole-4-acetate C02835 7273-34-9 O60 DL-beta-Hydroxyphenethylamine61 Urocanate C00785 104-98-3 O62 6-Hydroxynicotinate C01020 5006-66-6

63 Tropine C00729 64 4-Methyl-5-thiazoleethanol65 Spermidine C00315 124-20-9 O66 gamma-Guanidinobutyrate

67 Trientine C0716668 L-Lys C00047 56-87-1 O69 L-Gln C00064 56-85-9 O70 Acethylcholine71 Carbachol

72 L-Albizziine C08264 

73 Isatin C11129 74 L-Glu C00025 56-86-0 O75 O-Acetyl-L-serine C00979 66638-22-0 O76 D-Penicillamine77 L-Met C00073 63-68-3 O

78 2,6-Dimethylaniline C11004 79 3-Methyl adenine C00913 5142-23-4

80 Triethanolamine C0677181 Guanine C00242 73-40-5 O82 1-Adamantanamine83 3,4-Dihydroxyphenethylamine C03758 51-61-684 L-His C00135 71-00-1 O85 3-Indolyl acetonitrile C02938 771-51-7

86 Buformin C07674 87 Allantoin C01551 97-59-6 O88 Ibotenate89 Indole-3-acetaldehyde C00637 2591-98-2

90 Tolazoline C0714791 L-Carnitine C00318 44985-71-9 O92 3-Indole ethanol C00955 526-55-693 Nicotine C00745 54-11-594 Pterin C00715 2236-60-495 L-Phe C00079 63-91-2 O

96 Benzocaine C07527 

97 Phenylephrine C07441 98 Pyridoxal C00250 66-72-8

99 Mecamylamine C07511 100 Pyridoxine C00314 65-23-6

1011-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine C04599 

102 L-Arg C00062 74-79-3 O

103 N-Ethyl-L-Glutamine C01047 104 N-Acetyl-L-ornithine C00437 O

105 Gramine C08304 106 L-Citrulline C00327 372-75-8 O107 Fusarate

108 o-Phenanthroline C00604  109 L-Tyr C00082 60-18-4 O110 Quisqualate

111 Castanospermine C02256112 2,6-Diaminoheptanedioate C00680 O

113 Caffeine C07481

114L-beta-(3,4-dihydroxyphenyl)alanine(DOPA) C00355 

115 Thiabenbazole116 Spermine C00750 71-44-3 O117 L-Trp C00078 73-22-3 O118 Minoxidil119 Propiolate120 Acrylate C00511 79-10-7121 Glyoxylate C00048 298-12-4 O122 Propionate C00163 79-09-4 O123 Glycolate C00160 79-14-1 O124 Butyrate C00246 107-92-6 O

125 Pyruvate C00022 127-17-3 O126 Lactate C00186 79-33-4 O127 Thioglycolate C02086 68-11-1 O128 Chloroacetate129 Methanesulfonate 75-75-2 O130 Tiglate131 Isovalerate132 2-Oxobutyrate C00109 600-18-0 O133 Pentanoate C00803 109-52-4 O134 beta-Hydroxypyruvate C00168 1113-60-6135 beta-Hydroxybutyrate136 alpha-Hydroxybutyrate137 2-Hydroxyisobutyrate138 Malonate C00383 141-82-2139 Glycerate C00258 473-81-4 O140 Maleamate C01596 557-24-4141 Hexanoate C01585 142-62-1 O142 Fumarate C00122 110-17-8 O143 3-Methyl-2-oxobutanoate C00141 O144 Guanidoacetate145 Methylmalonate C02170 516-05-2 O146 Succinate C00042 110-15-6 O147 Benzoate C00180 65-85-0148 Isonicotinate149 Nicotinate C00253 59-67-6 O150 Diisopropyl phosphite151 L(+)-Tartarate C00898 87-69-4 O

152 2-Aminoethylphosphate153 (S)-(+)-1-Aminoethylphosphonate154 Citraconate C02226 498-23-7155 Itaconate 97-65-4156 Mesaconate C01732 498-24-8157 4-Methyl-2-oxovalerate C03589158 Glutarate C00489 110-94-1159 3-Ureido propionate160 Malate C00149 97-67-6 O161 p-Toluate C01454 99-94-5162 m-Toluate163 p-Hydroxybenzoate C00156 99-96-7164 m-Hydroxybenzoate C00587 99-06-9165 Salicylate C00805 69-72-7166 Acetyl phosphate C00227 19926-71-7 O167 Ethanolamine phosphate C00346 1071-23-4168 Valproate169 Caprylate170 2-Oxoglutarate C00026 328-50-7 O171 threo-b-Methyl-aspartate C03618 838-07-3172 trans-Cinnamate C00423173 2-Carboxybenzaldehyde C03057 119-67-5174 p-Hydroxyphenylacetate C00642 156-38-7175 L-Cysteine sulfinate176 2,5-Dihydroxybenzoate C00628 490-79-9177 Protocatechuate C00230 99-50-3178 Phenaceturate179 D-Glucuronate C00191 6556-12-3 O180 O-Hydroxyhippurate181 Gluconate C00257 526-95-4 O182 Erythrose 4-phosphate C00279 585-18-2 O183 Sebacate184 Indole-3-pyruvate C00331 35656-49-6185 Xanthurenate C02470 59-00-7186 Ibuprofen C01588 15687-27-1187 Etidronate C06985 7414-83-7188 DL-6,8-Thioctate amide189 DL-6,8-Thioctate, reduced190 Benzylsuccinate C09816 884-33-3191 N-Benzyloxycarbonylglycine C03710 1138-80-3192 Mucin C01357 9013-95-0193 2-Deoxyribose 5-phosphate194 4-Nitrophenyl phosphate C03360 330-13-2195 Pantothenate C00864 79-83-4 O196 Ribose 5-phosphate C00117 4300-28-1 O197 Ribulose 5-phopsphate C01101 4151-19-3 O198 Pyridoxal 5'-phosphate C00018 54-47-7 O199 D-Glucosamine 6-phosphate C00352 3616-42-0 O200 Fructose 6-phosphate C00085 643-13-0 O201 Glucose 1-phosphate C00103 59-56-3 O202 Glucose 6-phosphate C00092 56-73-5 O203 2,3-Diphosphoglycerate204 Gluconate 6-phosphate C00345 O205 Argininosuccinate C03406 O206 Nopaline C01682207 cTMP

208 cCMP 3616-08-8

209 dCMP C00239 1032-65-1 O210 dUMP C00365 964-26-1 O211 N-Acetylneuramate212 TMP C00364 365-07-1 O213 CMP C00055 84-52-6 O214 UMP C00105 58-97-9 O215 cAMP C00575 60-92-4216 Pyrroloquinoline guinone O217 dAMP C00360 653-63-4 O218 dIMP 3393-18-8 O219 Fructose 1,6-diphosphate C00354 488-69-7 O220 cGMP 7665-99-8221 AMP C00020 61-19-8 O222 dGMP C00362 902-04-5 O223 IMP C00130 131-99-7 O224 GMP C00144 85-32-5 O225 XMP C00655 523-98-8 O226 dCDP C00705 O227 Ribose 1,5-diphosphate C01151228 TDP229 CDP C00112 63-38-7 O230 UDP C00015 58-98-0 O231 dADP C00206 O232 ADP C00008 20398-34-9 O233 Adenosine 3',5'-diphosphate C00054 1053-73-2 O234 dGDP C00361 O235 Adenosine-5'phosphatesulfate C00224 O236 IDP C00104 86-04-4 O237 Isoguvacine (RBI)238 Octylamine C01740 111-86-4239 Oxoproline240 Cyanurate241 1-Amino-1-cyclopentane-carboxylate C03969 52-52-8242 1,1-Dimethyl biguanide243 N-Acetylputrescine C02714 18233-70-0244 Creatine C00300 57-00-1245 L-Ile C00407 73-32-5 O246 L-Leu C00123 61-90-5 O247 L-Hydroxyproline C01015 51-35-4248 delta-Aminolevulinate C00430 106-60-5 O249 epsilon-Amino-n-caproate250 L-Norleucine C01933 327-57-1251 beta-Guanidinopropionate252 L-Ornithine C01602 70-26-8 O253 L-Asn C00152 70-47-3 O254 D-Ornithine C00515 348-66-3255 4-Aminoindole256 5-Aminoindole257 Gly-Gly258 L-Asp C00049 56-84-8 O259 Adenine C00147 73-24-5 O260 2-Aminoimidazole261 DL-Homocysteine C00155 6027-13-0 O262 Hypoxanthine C00262 68-94-0 O263 Pralidoxime264 Tyramine C00483 51-67-2265 Anthranilate C00108 118-92-3 O

266 p-Aminobenzoate C00568 150-13-0 O267 Zalcitabine268 Pherazopyridine269 Bactofen270 Harmaline C06536 304-21-2271 N-Acetyl-D(+)-glucosamine C00140 7512-17-6 O272 Cystathionine C02291 56-88-2 O273 L-Carnosine C00386 305-84-0274 Porphobilinogen C00931 487-90-1 O275 2'-Deoxyuridine C00526 951-78-0 O276 L-Homocarnosine C00884277 Thymidine C00214 50-89-5 O278 Cytidine C00475 65-46-3 O279 Uridine C00299 58-96-8 O280 Octopine C04137 34522-32-2281 Adenosine C00212 58-61-7 O282 Inosine C00294 58-63-9 O283 Eserine284 Guanosine C00387 118-00-3 O285 Nopaline C01682286 Glutathione C00051 70-18-8 O287 Neamine C01441 3947-65-7288 S-Adenosyl-L-homocystein C00021 979-92-0 O289 Leu-Leu-Tyr290 Leupeptin C01591 288-32-4291 Piperacillin292 Dihydroorotate C00337 5988-19-2 O293 Acetylcysteine C06809 616-91-1294 p-Coumarate C00811 501-98-4295 o-Coumarate O296 beta-Phenylpyruvate297 3,4-Dihydroxyphenylacetate C01161 102-32-9298 Phosphoenol pyruvate C00074 138-08-9 O299 L-Cysteate C00506 13100-82-8 O300 Glyphosate C01705 1071-83-6301 Dihydroxyacetone phosphate C00111 57-04-5 O302 Glycerol 3-phosphate C00093 57-03-4 O303 2-Quinolinecarboxylate C6325 93-10-7304 cis-Aconitate C00417 585-84-2305 Phenyl phosphate C02734 701-64-4306 (-)Shikimate C00493 138-59-0 O307 Ascorbate C00072 50-81-7308 Carbamoylaspartate309 S-Carboxymethyl-L-cysteine310 Glucose C00031 50-99-7 O311 p-hydroxyphenylpyruvate C01179 O312 Dihydrocafeate313 O-Phospho-L-serine C01005 407-41-0 O314 3-Phosphoglycerate C00197 O315 2-Phosphoglycerate316 Azelaate317 N-Acetyl-L-glutamate C00624 1188-37-0 O318 N-Acetyl-L-methionine C02712 65-82-7319 Citrate C00158 77-92-9 O320 iso-Citrate C00311 30810-51-6 O321 GDP C00035 146-91-8 O322 7,8-Dihydrofolate C00415 4033-27-6 O

323 Flavin mononucleotide (FMN) 146-17-8 O324 Adenylosuccinate C03794325 dCTP C00458 2056-98-6 O326 dUTP C00460 O327 TTP C00459 O328 CTP C00063 65-47-4 O329 UTP C00075 63-39-8 O330 dATP C00131 1927-31-7 O331 dITP C01345 66701-25-5332 ATP C00002 56-65-5 O333 dGTP C00286 2564-35-4 O334 ITP C00081 132-06-9 O335 GTP C00044 86-01-1 O336 UDP-glucose C00029 O337 UDP-glucuronate C00167 O338 GDP-mannose C00096339 UDP-N-acetylglucosamine C00043 O340 CMP-N-acetylneuramate341 NAD C00003 53-84-9 O342 NADH C00004 53-84-9 O343 NADP C00006 53-59-8 O344 NADPH C00005 2646-71-1 O345 CoA C00010 85-61-0 O346 FAD C00016 146-14-5 O347 Acetyl-CoA C00024 72-89-9 O348 Propionyl CoA C00100 317-66-8 O349 Malonyl CoA C00083 524-14-1 O350 Succinyl CoA C00091 604-98-8 O