1
Supplement to Nature Publishing Group journals %GNNU JCXG GXQNXGF C O[TKCF QH TGIWNCVQT[ EKTEWKVU t HTQO VTCPUETKRVKQPCN VQ RQUVVTCPUNCVKQPCN t HQT UGPUKPI CPF TGURQPFKPI VQ FKXGTUG GPXKTQPOGPVCN UKIPCNU 5[PVJGVKE DKQNQI[ CKOU VQ TGGPIKPGGT VJGUG EKTEWKVU CPF EKTEWKV EQORQPGPVU VQ DTKPI CDQWV PQXGN UGPUQT[ HWPEVKQPU CPF VQ RTQEGUU VJG WRUVTGCO UKIPCNU KP RTGFKEVKXG YC[U HQT OQDKNK\KPI CRRTQRTKCVG EGNNWNCT TGURQPUGU #7) 'PXKTQPOGPVTGURQPUKXG RTQOQVGT 5GPUKVKXG GNGOGPV 6TCPUFWEGT OQFWNG )GPG )GPG )GPG 2 2 #RVCOGT FQOCKP 4GIWNCVQT[ FQOCKPU CPVKUGPUG TKDQ\[OGU GVE • 'PIKPGGTGF IGPG EKTEWKVU • 6TCPUETKRVKQPCN EJCPIGU 2TQVGKP TGEGRVQT • 4GURQPUG TGIWNCVQTU • 5KIPCN VTCPUFWEVKQP 2QUVVTCPUNCVKQPCN &GUKIP RTKPEKRNG 6TCPUETKRVKQPCN 6TCPUNCVKQPCN 2 +PRWV 1WVRWV 5[PVJGVKE UGPUKPI 5[PVJGVKE CRRTQCEJGU JCXG DGGP WUGF VQ FGXGNQR EGNNWNCT QRVKECN UGPUQTU *CTPGUUKPI CPF TGGPIKPGGTKPI E[CPQDCEVGTKCN CPF RNCPVFGTKXGF RJQVQTGEGRVKXG FQOCKPU JCU WPNQEMGF C XCTKGV[ QH NKIJVUGPUKVKXG CRRNKECVKQPU KPENWFKPI 'UEJGTKEJKC EQNK DCUGF KOCIGGFIG FGVGEVKQP NGȎ CPF QRVKECN EQPVTQN QH OCOOCNKCP EGNN RTQEGUUGU TKIJV +P VJG NCVVGT GZCORNG VJG QRVKECN EQPVTQN QH EGNN OQVKNKV[ YCU FGOQPUVTCVGF D[ HQEWUKPI TGF NKIJV QP C UOCNN RQTVKQP QH VJG EGNN EKTENG #U C TGUWNV RTQVGKP FQOCKPU VJCV OQFKH[ VJG CEVKP E[VQUMGNGVQP YGTG URCVKCNN[ TGETWKVGF VQ KPFWEG VJG NQECN GZVTWUKQP QH NCOGNNKRQFKC KP NKXG EGNNU 2 %JKOGTKE UGPUQT .KIJV QT FCTM OKP OKP OKP OKP OKP OKP 1RVKECN EQPVTQN QH EGNN RTQEGUUGU +OCIGGFIG FGVGEVKQP OKP OKP OKP OKP OKP OKP 2TQVGKP UECȭQNFU YJKEJ UGTXG CU PCVWTCN UKIPCN RTQEGUUKPI JWDU ECP DG RWTRQUGHWNN[ GPIKPGGTGF VQ VWPG VJG QWVRWV TGURQPUG QH EGNNU VQ GPXKTQPOGPVCN QT KPVGTPCN UKIPCNU +P VJG GZCORNG UJQYP C U[PVJGVKE RTQVGKP UECȭQNF YCU WUGF VQ RJ[UKECNN[ TGETWKV RQUKVKXG CPF PGICVKXG OQFWNCVQTU QH C /#2 MKPCUG RCVJYC[ VQ GPCDNG PGY CPF FGUKTGF EKTEWKV TGURQPUGU HQT GZCORNG CEEGNGTCVGF FGNC[GF QT WNVTCUGPUKVKXG TGURQPUGU 1WV +P 1WV s 5[PVJGVKE PGICVKXG HGGFDCEM 5[PVJGVKE RQUKVKXG HGGFDCEM $KQUGPUKPI 5[PVJGVKE UKIPCN RTQEGUUKPI .GWEKPG \KRRGTU .GWEKPG \KRRGTU 0WENGWU 6JG WUG QH U[PVJGVKE CRRTQCEJGU HQT EQPUVTWEVKPI CPF QRVKOK\KPI DKQU[PVJGVKE RCVJYC[U KU RTQXKFKPI CP CNVGTPCVKXG CPF EQUVGȭ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ȮECVKQP CPF UGNGEVKQP QH RCVJYC[ EQORQPGPVU HQT QRVKOK\GF RCVJYC[ ȯWZ +P VJG GZCORNG UJQYP VJG ' EQNK FGQZ[Z[NWNQUG RJQURJCVG &:2 RCVJYC[ YCU OQFKȮGF KP XKXQ VQ CEJKGXG OCZKOCN N[EQRGPG RTQFWEVKQP &:2 5WDUVTCVGU (CTPGU[N FKRJQURJCVG 'P\[OG 'P\[OG 4GEQXGT[ 1NKIQPWENGQVKFGU .[EQRGPG #TVGOKUKPKP )GPQOG 1RVKOK\KPI RCVJYC[ ȯWZ GXQNWVKQPCT[ FGUKIP 4GRNCEGOGPV 4GRNCEGOGPV )TQYVJ )TQYVJ &:2 RCVJYC[ #EGV[N%Q# /GXCNQPCVG RCVJYC[ VQR QRGTQP Enzyme 1 Enzyme 2 Enzyme 3 Scaffold Scaffold /GXCNQPCVG /GVCDQNKE ȯWZ ECP CNUQ DG EQPVTQNNGF YKVJ TCVKQPCN FGUKIP t HQT KPUVCPEG D[ URCVKCNN[ TGETWKVKPI VJG GP\[OGU EQORTKUKPI C DKQU[PVJGVKE RCVJYC[ VQ C U[PVJGVKE RTQVGKP UECȭQNF Enzyme 1 Enzyme 2 Enzyme 3 1RVKOK\KPI RCVJYC[ ȯWZ TCVKQPCN FGUKIP 5[PVJGVKE DKQNQI[ YCU DQTP YKVJ VJG DTQCF IQCN QH nYKTKPIo DKQNQIKECN EKTEWKVT[ HQT OCPKHGUVKPI NQIKECN HQTOU QH EGNNWNCT EQPVTQN 6JG UWEEGUUHWN FGUKIP CPF EQPUVTWEVKQP QH GCTN[ U[PVJGVKE IGPG PGVYQTMU t HQT GZCORNG VJG IGPGVKE VQIING UYKVEJ CPF VJG TGRTGUUKNCVQT t FGOQPUVTCVGF VJCV GPIKPGGTKPIDCUGF OGVJQFQNQI[ EQWNF KPFGGF DG CRRNKGF VQ DWKNF RTGFKEVKXG CPF UQRJKUVKECVGF DGJCXKQWT KPVQ DKQNQIKECN U[UVGOU +P VJG UKORNG FGXKEGU UJQYP EGNNU YGTG RTQITCOOGF VQ VQIING DGVYGGP UVCDNG IGPGVKE UVCVGU NGȎ CPF VQ RGTHQTO IGPGVKE VCUMU RGTKQFKECNN[ TKIJV +P C NKVVNG QXGT [GCTU VJG ȮGNF JCU OQXGF C NQPI YC[ HTQO VJGUG DCUKE DGIKPPKPIU 5[PVJGVKE DKQNQI[ HQWPFCVKQPU lacI tetR cl lacI tetR 6QIING UYKVEJ 4GRTGUUKNCVQT 'PIKPGGTGF RTQVGKP UECȭQNF +P 5[PVJGVKE EKTEWKVU QȭGT C OQTG EQPVTQNNGF CRRTQCEJ VQ IGPG VJGTCR[ UWEJ CU VJG CDKNKV[ VQ F[PCOKECNN[ UKNGPEG CEVKXCVG CPF VWPG VJG GZRTGUUKQP QH FGUKTGF IGPGU +P VJG GZCORNG UJQYP C IGPGVKE UYKVEJ YCU FGXGNQRGF KP OCOOCNKCP EGNNU VJCV EQWRNGU VTCPUETKRVKQPCN TGRTGUUQT RTQVGKPU CPF CP 40#K OQFWNG HQT VKIJV VWPCDNG CPF TGXGTUKDNG EQPVTQN QXGT VJG GZRTGUUKQP QH FGUKTGF IGPGU 1(( lacI tetR RNAi Gene RNAi target lacI tetR RNAi Gene RNAi target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ȮECVKQP &GXKEGU HQT U[UVGOCVKECNN[ RGTVWTDKPI CPF RTQDKPI VJG HWPEVKQP QH KPFKXKFWCN EQORQPGPVU QH C PCVWTCN RCVJYC[ &KUGCUG OGEJCPKUO KFGPVKȮECVKQP (TCOGYQTMU HQT U[PVJGVKECNN[ TGEQPUVTWEVKPI PCVWTCN U[UVGOU VQ GZRNQTG JQY RCVJQNQIKECN DGJCXKQWTU GOGTIG 6JGTCRGWVKE VTGCVOGPV 'PIKPGGTGF XKTWUGU CPF QTICPKUOU VJCV VCTIGV URGEKȮE RCVJQIGPKE CIGPVU CPF EQTTGEV RCVJQNQIKECN OGEJCPKUOU 6JGTCRGWVKE URGEVTWO HTQO FKUGCUG KFGPVKȮECVKQP VQ FTWI RTQFWEVKQP 5[PVJGVKE DKQNQI[ FGXKEGU JCXG DGGP FGXGNQRGF VQ UGTXG CU VJGTCRKGU VJGOUGNXGU +P VJKU GZCORNG GPIKPGGTGF DCEVGTKQRJCIGU JCXG DGGP FGRNQ[GF VQ EQODCV VJG ITQYKPI RTQDNGO QH CPVKDKQVKETGUKUVCPV DCEVGTKC $CEVGTKQRJCIGU YGTG U[PVJGVKECNN[ GPFQYGF YKVJ C IGPGVKE CTOCOGPV FKURGTUKP $ &UR$ VJCV GȭGEVKXGN[ RGPGVTCVGU CPF FGUVTQ[U VJG CPVKDKQVKERTQVGEVGF GPXKTQPOGPV MPQYP CU C DKQȮNO 6JGTCRGWVKE VTGCVOGPV +PKVKCN KPHGEVKQP &UR$ 'PIKPGGTGF &UR$GZRTGUUKPI 6 RJCIG $CEVGTKQRJCIG TGRNKECVKQP CPF &UR$ GZRTGUUKQP %QPVKPWGF KPHGEVKQP %GNN N[UKU RJCIG CPF &UR$ TGNGCUG CPF DKQȮNO FKURGTUCN Synthetic biology: applications come of age Ahmad S. Khalil and James J. Collins Synthetic biology is bringing together engineers and biologists to design and build novel biomolecular components, networks and pathways and to use these constructs to rewire and reprogram organisms. These re-engineered organisms will change our lives over the coming years, leading to cheaper drugs, ‘green’ means to fuel our cars and targeted therapies for attacking ‘superbugs’ and diseases such as cancer. The de novo engineering of genetic circuits, biological modules and synthetic pathways is beginning to address these crucial problems and is being used in related practical applications 1 . GENETICS Image credits Synthetic biology foundations: Modified from REF. 1 © Macmillan Publishers Ltd. | Biosensing: Modified from REF. 1 © Macmillan Publishers Ltd. | Synthetic signal processing: Modified from REF. 6 © AAAS | Synthetic Sensing: Modified from REF. 1 © Macmillan Publishers Ltd., REF. 7 © Elsevier and REF. 8 © Macmillan Publishers Ltd. | Therapeutics: Modified from REF. 1 © Macmillan Publishers Ltd. | Therapeutic treatment: Modified from REF. 9 © NAS | Controlled gene expression: Modified from REF. 1 © Macmillan Publishers Ltd. | Manufacturing: Modified from REF. 1 © Macmillan Publishers Ltd. | Optimizing pathway flux: rational design: Modified from REF. 1 © Macmillan Publishers Ltd. | Optimizing pathway flux: evolutionary design: Modified from REF. 1 © Macmillan Publishers Ltd. Acknowledgements A.S.K. and J.J.C. thank the Howard Hughes Medical Institute and the US National Institutes of Health Director’s Pioneer Award for their support. Edited by Tanita Casci; copy-edited by Matthew Smyllie; designed by Patrick Morgan © 2011 Nature Publishing Group. http://www.nature.com/ nrg/posters/synbioapps References 1 Khalil, A. S. & Collins, J. J. Nature Rev. Genet. 11, 367–379 (2010) | 2 Gardner, T. S., Cantor, C. R. & Collins, J. J. Nature 403, 339–342 (2000) | 3 Elowitz, M. B. & Leibler, S. Nature 403, 335–338 (2000) | 4 Bayer, T. S. & Smolke, C. D. Nature Biotech. 23, 337–343 (2005) | 5 Culler, S. J., Hoff, K. G. & Smolke, C. D. Science 26, 1251–1255 (2010) | 6 Bashor, C. J., Helman, N. C., Yan, S. & Lim, W. A. Science 319, 1539–1543 (2008) | 7 Tabor, J. J. et al. Cell 137, 1272–1281 (2009) | 8 Levskaya, A., Weiner, O. D., Lim, W. A. & Voigt, C. A. Nature 461, 997–1001 (2009) | 9 Lu, T. K. & Collins, J. J. Proc. Natl Acad. Sci. USA 104, 11197–11202 (2007) | 10 Deans, T. L., Cantor, C. R. & Collins, J. J. Cell 130, 363–372 (2007) | 11 Ro, D. K. et al. Nature 440, 940–943 (2006) | 12 Wang, H. H. et al. Nature 460, 894–898 (2009) | 13 Martin, V. J., Pitera, D. J., Withers, S. T., Newman, J. D. & Keasling, J. D. Nature Biotech. 21, 796–802 (2003) | 14 Dean, J. T. et al. Cell Metab. 9, 525–536 (2009) | 15 Weber, W. et al. Proc. Natl Acad. Sci. USA 105, 9994–9998 (2008) Blue Heron — Leading Gene Synthesis Technologies for Synthetic Biology Applications Blue Heron Biotech has been a pioneer of the gene synthesis industry since 1999. Through the years, Blue Heron has developed novel and proprietary high throughput, fully automated synthesis platforms to serve customers who need a single gene to megabases of DNA. Part of that pioneering activity has led Blue Heron to be the first company to: • Work with researchers worldwide to create synthetic DNA components • The primary supplier for the first synthetic genome, as published in Science (Gibson, D. G. et al. 329, 52–56 (2010)) • Deliver a 52 kb gene • Synthesize a megabase of DNA in a month Innovation for the Synthetic Biology Researcher Blue Heron offers breakthrough technologies to meet the growing synthesis demands of researchers worldwide. These innovations include expanding capabilities for: • Complex sequence synthesis • Shuffling of synthetic blocks • Variant libraries • Whole-genome synthesis Blue Heron is Your Gene Synthesis Partner In August 2010, Blue Heron became a wholly owned subsidiary of OriGene Technologies, Inc. Together we can now provide a one-stop solution for the molecular biology research community. For more information: www.blueheronbio.com or www.origene.com Blue Heron Biotech, LLC 1-425-5000 Bothell, Washington, USA nrg_poster_jul11.indd 1 16/06/2011 10:19
