Examples of Industrial Biotechnology in the Chemistry-using Industries

8/18/2019 Examples of Industrial Biotechnology in the Chemistry-using Industries

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Examples of Industrial Biotechnology in the

Chemistry-using Industries


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Peptides: Hydrolases

HOOC

COOH

NHZ H2N COOMe

CH2Ph

1. Thermolysin

2. H2 / Cat.

+ HOOCHN COOMe

NH2

O CH2Ph

ASPARTIC ACID PHENYL ALANINE ASPARTAME

L

DL

L

L

200 TIMES SWEETER THAN SUCROSE

• Great example of Regio- and Enantioselectivity

• DSM / TOSOH (HOLLAND SWEETNER CO) : multi thousand t/a

• Old chemical method by Searle – protection / deprotection

• more expensive

ASPARTAME – artificial sweetener: using Proteases


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Antibiotics : Hydrolases

‘ DYNAMIC RESOLUTION ’

• 100% conversion to a single isomer

• Intermediate for β-Lactam antibiotics - Amoxicillin / Cephadroxil

• KANEGAFUCHI / DSM / SNAM Progetti / GSK : > 8,000 t/a

D-HYDROXYPHENYLGLYCINE : Two steps – Two enzymes


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Pharma: Ligases / Synthetases

• A natural alkaloid - anti-asthmatic and for blood circulation disorders

• Reaction discovered in 1921

• Industrial production by KNOLL, Malladi (India) etc.

L-EPHEDRINE : Chiral condensation / C-C bond formation


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• Energy consumption reduced by 60%

• Emission of pollutants reduced by 60-90%

• Emission of greenhouse gases reduced by 62%

Chemical process: 5 purification steps: temp: up to 240OC

Biocatalytic process: 0 purification steps: temp: up to 60OC

IFSCC Congress 2006, Degussa & Novozymes

Myristyl myristate : Emollients - Simple Esterification

Speciality Chemicals: Cosmetics


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Bulk Chemicals: Nitrile hydratase

Mitsubishi Rayon (formerly Nitto Japan) and Others : ca. 300,000 t/a (of total 500,000 t/a)

Single largest commodity chemical manufacture through Biocatalysis

Acrylamide : Bulk Chemical Production

Sulfuric acid hydration process 1950s - 1970s

Copper catalyst process 1970s - 1980s

Enzymatic process since 1985


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Cleaner Cheaper Chemistry

• Increased yield

• Reduced environmental impact

• Replacement of hazardous operations

• Reduced cost (No organic solvent, ambient temp)

• Reduced reactor time

On a manufacturing scale, 3 tons of palladium catalyst per year

replaced with 150 kg of immobilised enzyme.

Lotrafiban scale-up;

GSK

Replacement of Pd catalyst, used at 70oC, in organic solvent, in a high

pressure hydrogenation.


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Chiral Alcohols

• Lipase catalysed Kinetic resolution

• A well-established platform now

• Several major applications

― Intermediates in Pharma, Agchem, Fragrance etc

Enzymes in Organic Solvents! A groundbreaking discovery!!


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‘Fatty’ Dicarboxylic acids

CATHAY INDUSTRIAL BIOTECH

• C11 Undecanedioc acid

• C12 Dodecanedioic acid

• C13 Brasyllic acid

• C14 Tetradecanedioic acid

• C15 Pentadecanedioic acid

• C16 Hexadecanedioic acid

• Trial production

FATTY ACIDS DIACIDS

CH3 – (CH2)n – CH3

FERMENTATION

HOOC – (CH2)n – COOH

n = C9 – C14

Various applications

Omega oxidation of alkanes


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From ‘natural’ Ferulic acid & ‘natural’ biocatalysts

CO2H

OH

OMe OMe

OH

CHO

Made by Givaudan, Rhodia, SAFISIS and others

• Natural Ferulic acid available from rice, maize etc and cheaper than vanillin.

• “Oxidative cleavage” : enzymatic hydration and retro-aldol.

• Occurs in whole cells – bacteria & fungi

‘Natural’ Vanillin

2% w/w in vanilla beans

0.2% w/w in vanilla extract

Natural vanillin : ~ $4,000 / kg

Synthetic : ~ $25 / kg


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Corn to Polyesters

1,3 – Propanediol

• Renewable resource content of Sorona : 37%

DuPONT-GENENCOR VENTURE


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Corn to Polylactic acid

DOW-CARGILL VENTURE

First large scale production by NatureWorks

• First plant - 14,000 t/a in NEBRASKA (US) in 2000-01 / $300 M investment

• Produced by several other companies now

•Several applications now in place

―Though more expensive than petroleum derived commodity plastics


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Sugar cane to tyres......

Process involves

• Microbial strain development

•

Large scale fermentation• Recovery and purification

Genencor, a Division of Danisco, has developed technology for manufacturingisoprene from sugar cane, corn, corn cobs, switchgrass or other biomass,

•

The vision is that all Goodyear tyres will be manufactured from this bio-isoprene

• Manufacturing a conventional tyre requires 7 gallons of petroleum feedstock per tyre.

•Using bio-isoprene will reduce that down to close to zero

http://upload.wikimedia.org/wikipedia/commons/5/50/Isoprene.svghttp://upload.wikimedia.org/wikipedia/commons/5/50/Isoprene.svg


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Bio-succinic acid

From glucose / renewable resources, not maleic acid

• Bio-amber started production

• DSM + Roquette pilot scale 2010, commercial 2011

• Market for succinic acid estimated at €2.5 billion

• Uses: in antifreeze liquids, coolants, solvents, pigments, polyesters, butanediol

and its derivatives, plasticizers, etc.

http://www.google.co.uk/imgres?imgurl=http://www.stockwatch.in/files/petroleum.jpg&imgrefurl=http://www.stockwatch.in/energy-sector-and-oil-futures-update-commodity-traders-nirmal-bang-22183&usg=__9OlVHIAs-2Fk2yxuWgpZvTOT4uE=&h=611&w=840&sz=90&hl=en&start=1&um=1&itbs=1&tbnid=9UNcMZCqVOZsPM:&tbnh=105&tbnw=145&prev=/images?q=petroleum&um=1&hl=en&sa=N&tbs=isch:1


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Bio-1,4-Butanediol

• Replacing Acetylene + Formaldehyde ---> 1,4-Butynediol ---> 1,4-Butanediol

•

Claims: reduction of 25% of GHG emissions and 30% reduction in direct energy• Estimated current global BDO market: $3billion

• 3000L scale tried at Michigan Biotechnology Institute

• Plans : demonstration facility 20-50kL by 2011, and commercial production 2013-2014

Use cellulosic biomass and syngas as future feedstock

u rose

BIO-1,4-BUTANEDIOL

Spandex

Automotive parts

Running shoes

Cheaper & Greener Bio-Butadiene?

Single step

Gen. Eng. E. Coli

GENOMATICA (BIO June 2010)


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‘Rubbish’ to bio-ethanol

• Convert low cost biomass & wastes (MSW) to clean fuel and energy

• Deliver a step change in green house gas emissions

• Achieve both in a safe, reliable, cost effective & sustainable way

Bioethanol

Renewable

powerFeedstock

flexible

Gasification

Fermentation

BIOMASS SYNGAS BIOETHANOL


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C2 Platform - Ethanol

EthyleneEthyl tert -butyl ether

Ethyl esters

Ethyl ethers

Glycol ethersEthylamine

Acetaldehyde

Bio-POLYETHYLENE / PVC / PVABraskem / Dow / Solvay / Wacker


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C3 Platform - Glycerol

Epichlorohydrin

1,2-propanediol 1,3-Propanediol

Mono-, di- and tri-esters Polyglycerols & Polyglycerol esters

Glyceric acid

Acrolein

http://www.google.co.uk/imgres?imgurl=http://sabimex.com/uploads/product/vegetable-oil-consultants-col.jpg&imgrefurl=http://sabimex.com/english/items.asp?id=39&usg=__dj0E1zhMR1oN2UjYfZYsXK4jD2A=&h=241&w=315&sz=18&hl=en&start=16&um=1&itbs=1&tbnid=sv-7Z-cx7FMD-M:&tbnh=90&tbnw=117&prev=/images?q=vegetable+oil&um=1&hl=en&tbs=isch:1


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C4 Platform – Succinic acid

Polyesters

Polyamides

1,4-Butanediol

-Butyrolactone

Tetrahydrofuran

N-Methyl-2-pyrrolidone (NMP)

Di-esters


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Arrange a visit from the Industrial Biotechnology SectorExpert Dr Yvonne Armitage to see how IB can help you

and your business

[email protected]

_connect up with the Industrial Biotechnology Special

Interest Group online

https://ktn.innovate.org/web/industrial-biotechnology

Documents

Examples of Industrial Biotechnology in the Chemistry-using Industries