Examples of Industrial Biotechnology in the
Chemistry-using Industries
Peptides: Hydrolases
ASPARTAME – artificial sweetener: using Proteases
NHZ
+
H2N
DL
NH2
COOMe
HOOC
L
COOH
ASPARTIC ACID
1. Thermolysin
2. H2 / Cat.
CH2Ph
PHENYL ALANINE
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
H
N
HOOC
L
COOMe
L
O
ASPARTAME
CH2Ph
Antibiotics : Hydrolases
D-HYDROXYPHENYLGLYCINE : Two steps – Two enzymes
‘DYNAMIC RESOLUTION’
• 100% conversion to a single isomer
• Intermediate for β-Lactam antibiotics - Amoxicillin / Cephadroxil
• KANEGAFUCHI / DSM / SNAM Progetti / GSK : > 8,000 t/a
Pharma: Ligases / Synthetases
L-EPHEDRINE : Chiral condensation / C-C bond formation
• A natural alkaloid - anti-asthmatic and for blood circulation disorders
• Reaction discovered in 1921
• Industrial production by KNOLL, Malladi (India) etc.
Speciality Chemicals: Cosmetics
Myristyl myristate : Emollients - Simple Esterification
• 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
Bulk Chemicals: Nitrile hydratase
Acrylamide : Bulk Chemical Production
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
Sulfuric acid hydration process 1950s - 1970s
Copper catalyst process
1970s - 1980s
Enzymatic process
since 1985
Cleaner Cheaper Chemistry
Replacement of Pd catalyst, used at 70oC, in organic solvent, in a high
pressure hydrogenation.
Lotrafiban scale-up;
GSK
•
•
•
•
•
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.
Chiral Alcohols
Enzymes in Organic Solvents!
 A groundbreaking discovery!!
•
Lipase catalysed Kinetic resolution
•
A well-established platform now
•
Several major applications
― Intermediates in Pharma, Agchem, Fragrance etc
‘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
Omega oxidation of alkanes
CH3 – (CH2)n – CH3
FERMENTATION
HOOC – (CH2)n – COOH
n = C9 – C14
Various applications
‘Natural’ Vanillin
From ‘natural’ Ferulic acid & ‘natural’ biocatalysts
CO2H
2% w/w in vanilla beans
0.2% w/w in vanilla extract
CHO
OMe
OMe
OH
OH
Natural vanillin : ~ $4,000 / kg
Synthetic
: ~ $25 / kg
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
Corn to Polyesters
1,3 – Propanediol
DuPONT-GENENCOR VENTURE
• Renewable resource content of Sorona : 37%
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
Sugar cane to tyres......
Genencor, a Division of Danisco, has developed technology for manufacturing
isoprene from sugar cane, corn, corn cobs, switchgrass or other biomass,
Process involves
• Microbial strain development
• Large scale fermentation
• Recovery and purification
•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
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.
Bio-1,4-Butanediol
Gen. Eng. E. Coli
Sucrose
Single step
GENOMATICA (BIO June 2010)
BIO-1,4-BUTANEDIOL
Spandex
Automotive parts
Running shoes
Cheaper & Greener Bio-Butadiene?
• 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
‘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
BIOMASS
Feedstock
flexible
SYNGAS
BIOETHANOL
Renewable
power
Bioethanol
Fermentation
Gasification
C2 Platform - Ethanol
Ethyl tert-butyl ether
Ethylene
Bio-POLYETHYLENE / PVC / PVA
Braskem / Dow / Solvay / Wacker
Ethyl esters
Ethyl ethers
Acetaldehyde
Ethylamine
Glycol ethers
C3 Platform - Glycerol
1,2-propanediol
1,3-Propanediol
Glyceric acid
Epichlorohydrin
Acrolein
Mono-, di- and tri-esters
Polyglycerols & Polyglycerol esters
C4 Platform – Succinic acid
Tetrahydrofuran
1,4-Butanediol
Polyesters
N-Methyl-2-pyrrolidone (NMP)
Polyamides
-Butyrolactone
Di-esters
Arrange a visit from the Industrial Biotechnology Sector
Expert 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