Enzymes in green chemistry

Suresh Kumar Kannapogu

Project-Leader 21/02/2017

About us

• Pioneered enzyme production in India in 1958

• Leading producer of enzymes in Asia

• Exports to 45+ countries across 6 continents

• 60+ enzymes and 360+ products

• Safe, eco-friendly and biodegradable solutions for 25+ industries

• State-of-the-art manufacturing facilities that are ISO and WHO cGMP

certified

Think of Life Think of Enzymes

Think of us!

History & Milestones 1958: India's first enzyme manufacturing plant (for Papain) is pioneered by Mr. L.C. Rathi

1978: Rathi Papains Pvt. Ltd. was incorporated

1986: Specialty Enzymes & Biotechnologies, United States is set up

1989: Advanced Enzymes is incorporated (Originally under the name of Advanced Biochemicals Pvt. Ltd. )

1994: Commissioning of our 1st fermentation facility at Sinnar, Maharashtra

2008: Commissioning of 2nd fermentation facility at Pithampur, Madhya Pradesh

2011: US Businesses operating under the name of Specialty Enzymes & Biotechnologies are consolidated under our subsidiary Advanced Enzymes USA

2016 : Listed in BSE & NSE. Only Enzyme Manufacturing Co. Listed.

Manufacturing Sites

• Fermentation, Recovery, Mixing & Blending facility at

Sinnar, Maharashtra, India

• Fermentation, Recovery, Mixing & Blending facility at

Pithampur,Madhya Pradesh, India

• Extraction & Recovery plant at Satpur, Maharashtra, India

• Mixing & Blending facility at Vashind, Maharashtra, India

• Two Mixing & Blending facilities at Chino, California, USA

Fermentation, Recovery, Mixing & Blending facility at Pithampur, Madhya Pradesh, India

Business Segments

What are Enzymes?

Enzymes are biological catalysts which

accelerates chemical reaction without being

consumed or changed.

Enzymes are Important tool in green

chemistry

• Enzymes have emerged as preferred tools in green

chemistry and increasingly used in industrial processes

due to their ability to catalyze reactions with high

catalytic efficiency and specificity.

• Today a Google search for ‘enzymes in green chemistry’

produces 20,00,000 results in 0.37 seconds showing

their importance.

Enzymes Growth

• The world market for enzyme production and application in chemical

sector is growing bigger every day,and the demand for useful

biocatalysts is increasing rapidly.

• As per business standard report the current enzyme market is 5.7

USD.

• By 2020 enzymes market will grow worth 7.2 Billion USD by 2020.

Importance of Enzymes in

Pharmaceutical Industry

• Enzymes process are much safer and easy to control than

chemical

• Avoidance of hazardous reagents.

• Enzymes works in aqueous and non aqueous media

• Enzymes operate under milder conditions( Ambient Temp, pH Etc)

• Enzymes offer high optical purity ,high chemo selectivity, high

regio- and stereo-selectivity.

• Enzymes produce no harmful by-products.

• Enzymes are biodegradable and reusable.

• High yield due to excellent selectivity

• Reduce number of manufacturing steps

Enzymes Vs Chemical reaction Parameter Chemical Biocatalysis

Manpower Requirement High Low

Power Consumption High Low

Solvent Requirement High Low

Specific Reactions Not Possible Possible

Yield of Desired Product Relatively Low Close to 100%

Need for Purification Very High Low

Effluent Load High Low

Processing Time Longer Shorter

Risk Involved in the

Process

High Low

Types of Enzymatic Reactions

Types of Enzymatic Reactions

Lock and Key Model

+ +

E + S ES complex E + P

S

P

P

S

Induced Fit Model

E + S ES complex E + P

S

P

P

S S

Misconceptions and Myths

Enzymes are highly unstable

Enzymes act only on natural substrates

Enzymes are too expensive

Productivity of Enzymes are too low

Pharma Applications

Pregabalin Intermediate

Cyano Route

EtOOC COOEt

CN

diethyl (1-cyano-3-methylbutyl)malonate

Lipase

-OOC COOEt

CN

EtOOC COOEt

CN

+

S-Enantiomer R-Enantiomer

To treat Epilepsy, Neuropathic pain

Pregabalin Intermediate

(Methyl Isobutyl Glutarate)

O CH3

CH3

MeO

O OH

O CH3

CH3

MeO

O OMe

(3S)-3-(2-methoxy-2-oxoethyl)-5-methylhexanoic acid

Lipase

dimethyl 3-(2-methylpropyl)pentanedioate

Prostaglandins Intermediate

OOO

CH3

OCH3

Lipase

OOHO

CH3

cyclopent-4-ene-1,3-diyl diacetate (1S,4R)-4-hydroxycyclopent-2-en-1-yl acetate

Platelet Aggregation inhibitor

Versatile building block (Ticagrelor/ Prostaglandins,

Prostacyclin's and Thromboxane )

Trandolapril Intermediate

LipaseCOOMe

COOMe

dimethyl cyclohexane-1,2-dicarboxylate

COOH

COOMe

(1S,2R)-2-(methoxycarbonyl)cyclohexanecarboxylic acid

Ace Inhibitor, Anti Hypertensive

Darunavir Intermediate

O

O

OCH3

O

O

O

H OCH3

O

Hhexahydrofuro[2,3-b]furan-3-yl acetate (3R,3aS,6aR)-hexahyd

rofuro[2,3-b]furan-3-yl acetate

Lipase

O

O

H OH

H

+

(3S,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-ol

Anti Viral

Moxifloxacin(Nonane) Intermediate

dimethyl 1-acetylpiperidine-2,3-dicarboxylate

NO

OH

O CH3O

O

CH3N

O

O CH3

O

O

O

CH3

CH3

NO

O

O CH3O

O

CH3

CH3

dimethyl (2S,3R)-1-acetylpiperidine-2,3-d

icarboxylate

(2R,3S)-1-acetyl-2-(methoxycarbonyl)piperidine-3-carboxylic acid

+

Lipase

It is fourth-generation synthetic Fluoroquinolone antibacterial

Agent

Odanacatib Intermediate

CH2

O

N

O

CH3

CH3

F

CH3

CH3

F

CH2

O

NHCH3

N-[(2R)-4-fluoro-4-methylpentan-2-yl]pent-4-enamide

2-(but-3-en-1-yl)-4-(2-fluoro-2-methylpropyl)-1,3-oxazol-5(4H)-one

Lipase

Key Intermediate for Odanacatib

Osteoporosis and Bone Metastasis

L-Menthol

Various applications in pharma and cosmetics

CH3

CH3 CH3

O

O

5-methyl-2-(propan-2-yl)cyclohexyl benzoate

CH3

CH3 CH3

OH

(1R,2S,5R)-5-methyl-2-(propan-2-yl)cyclohexanol

(-)-Menthol

Lipase

Perindopril Intermediate

(Racemic)

ethyl indoline-2-carboxylate

NH

O

OHNH

O

O

CH3

+

ethyl (2R)-indoline-2-carboxylate (2S)-indoline-2-carboxylic acid

NH

O

O

CH3

Lipase

Treat high blood pressure

Lipases are versatile Biocatalyst

Our Enzymes are used in following areas

• Chiral Drug Intermediates

• Cosmetic Esters

• Flavors / Perfume Esters

• Fine Chemical Synthesis

• Emulsifiers

• Polymers

Lipases

- Candida Antartica Lipase A(CAL-A)

- Candida Antartica Lipase B(CAL-B)

- Thermomyces Lanuginosus Lipase (TL)

- Candida Rugosa Lipase (CRL)

- Rhizomucor Miehei Lipase

- Pancreas Lipase

Proteases

- Addzyme FP 500 - Addzyme AFP 300

- Addzyme BPS 200 -Addzyme BPN 200

- Addzyme LP 1000L -Addzyme DP 1000L

• Glucose Oxidase

• Celluloses

• Xylanases

Enzymes we offer for Biocatalysis

Our Lipases offerings Parameters Addzyme

Lipase Liquid

Addzyme

Powder

Addzyme

Immobilized

Colour Light Yellow to Brown White White Beeds

pH Stability 3-10 3-10 3-10

Temperature

Stability

40-50° C 30-50° C 60-80° C ( Non

Polar Solvents)

40-50° C ( Polar

Solvents)

Activity 7000 units/gm 10,000 units/gm 10,000 units/gm

Technological assessment

• We at Advanced Enzymes are manufacturing and

exporting the enzymes to the various applications for last

4 decades.

• Our technical and application lab is well equipped to

develop and resolve the technical queries.

• Supported by the Enzymes experts for the Industrial

applications.

• Talk to us for the new development and support.

Thank You