| Enzyme experience Energetic delivery

The biocatalysis expertsyou’ll enjoy working with

Maria BohlinAnalytical ChemistR&D

InnovationClients from all sectors challenge us to identify enzymes suitable for the requested chemical conversions and develop the reaction ready for the integration into the complete production workflow. We respond by creating patentable know-how they can own, whilst we can operate as their reliable bulk supplier.

Adopting our technology requires no specialist equipment or knowledge, which keeps our clients’ processes simple and their costs down.

ExperienceSince 1999, we’ve grown to specialize in developing processes, designing and optimizing routes and providing R&D screening services using our proprietary library of >600 enzymes.

Our services in this area include:

• Enzyme screening

• Enzyme development

- Cloning and gene discovery

- Characterization and description of genes for different enzymes and functions

- Using different expression systems

• Process development and enzyme manufacturing

- Ability to work with different organisms and enzymes

- Process know-how for industrial enzyme production

- Process optimization and technology transfer available

• Synthetic route development and consulting

• Analytical method development

PerformanceFrom bulk production to industrialization, our specialists offer your business more benefits:

• Shorter synthetic and alternate routes

• Reagents and solvents are biodegradable

• Typical side reactions are avoided, meaning few by-products and impurities

• High conversion, yield and enantiomeric excess

• Low enzyme and negligible cofactor costs

• Biocatalyst experts you’ll enjoy working with

Read on to learn more about the conversions and reaction parameters Cambrex can achieve for you…

We’re big on biocatalysis

• Substrate load 100-400g/l

• Simple technology and equipment/standard batch reaction

• Inexpensive enzymes for R and S alcohols available in any scale

• Excellent enantio purity (>99.8%)

• Complete and quick conversion in 6-12 hours

• Cost contribution of coenzyme NAD(P) <1€/kg product

• No expensive ingredients or solvents

• Easy work up and removal of enzyme

• Environmentally friendly

Core TechnologyKetoreductases (>230 enzymes)

Core TechnologyKetoreductases for multiple applications

2 3

R1 R2

high value chiral alcohol

OH

R1 R2

O

NAD(P)H

IEPox

NAD(P)

OHO

Small and halogenated compounds

CICI

CIF

FF

OH

OHOH

OH

Chiral Intermediates for API

O

OH

OH

OOH

SN

OH

OH

OCI

OH OH O

O

CN

OH OH O

OCI

OH

OEt

O

Statine side chains

OH OH

COOH

CH3

Steroids and Bile acids OH

O N

OHOH

O O

S S

Cyclic compounds

Diols

OH

OH

OH

OH

OH

O

CI

Complex and bulky compounds

NHO

Adam LanebjerAnalytical Chemist, QC

Quality

IEPox Toolbox>230 enzymes

Cambrex has developed and commercially manufactured APIs, intermediates and bulk chemicals using biocatalysis for over 15 years. As a result, our enzymes and processes are improving cost and the efficiency of manufacturing small molecules at multi-ton scale. Not just in pharmaceuticals and generics, but in everyday life – from cosmetics and fragrances to food flavorings.

• For conversion of racemic amines to chiral amines or access to keto compounds

Monoamine - or amino acid oxidases

• Substrate load 50-150g/l

• Simple technology and equipment/standard batch reaction

• Inexpensive enzymes for R and S amines available in any scale

• Excellent enantio purity (>99.8%)

• >90% conversion in 6-12 hours

• No expensive ingredients or solvents

• Easy work up and removal of enzyme

• Environmentally friendly

Core TechnologyTransaminases (>100 enzymes)

Special Biotransformations

Core TechnologyTransaminases for multiple applications

4 5

R1 R2

high value chiral amine

NH2

R1 R2

O

O

IEPAT

or Alanine

or Pyrovate

NH2

Aliphatic chiral amine

NH2

Amphetamine

NH2R

Aromatic amine

NH2

Cl

NH2R

NH2

OH

OR1

NH2

OHR1

NH2

OR

O

Alpha and beta amino acids / esters amino alcohols

O NH2

Cyclic compounds

NH2

NH

N

NH

Heterocyclic amine

R RO

OH

C N

NH2

H2O

C Nitrilase

R RO

NH2

C N

H2O

C Nitrile hydratase

RROO

OHNH2

H2O

CC Amidase

R R

NADPH

NADP

NO2 NH2 Nitroreductase

NH2O

NH2

R

O

OHR

O

O

OHH2O

H2O2NH3

DAAO SaaT

NH2

OH

Cl O

DL-2-chlorophenylglycine

OH

Cl O

O

2-(chlorophenyl)acetic acid

NH2

OH

Cl O

L-2-chlorophenylglycine

Johan MattssonAnalytical Chemist

R&D

Anna GranbergAnalytical Chemist, QC

Quality

IEPox Toolbox>100 enzymes

Example

Amino acid oxidase/Monoamine oxidase

Nitrilases/Nitrile hydratases/Amidases/Nitroreductases

2

• Lactate oxidases

• Glycolate oxidases

• Azoreductases

• Halohydrin dehalogenases

• Aldolases (N-Acetylneuraminic acid lyase)

• ENE-Reductases

And many others

• Substrate concentration 50 up to 120g/l

• Simple technology and equipment

• Inexpensive enzyme, recombinant over-expressed (<10€/kg product)

• >95% conversion in 24 hours

• Cost contribution of co-enzyme <5€/kg product

• No expensive ingredients or solvents

• Easy work up and removal of enzyme

• Environmentally friendly

Delta1/Delta4 Dehydrogenation

Nitrilases

Esterases/Lipases and Hydrolases

6 7

CNS CN

CN

CN

OHCN

CNN

NOH

NO

CN

CN

O

O

HH

H

O

O

HH

H

Androsten-3,17 -dione H2O2 O2

IEPDD

acceptor

acceptor H2

H2OR2

R1 COOR3

R2

R1 COOR3

R1

COOR3

R1

COOH

R2

R1 COOH

R1

COOR3

+

+

Sibel AslanAnalytical Development Manager, R&D

Analytical Development

• Substrate concentration 100g/l

• Simple technology and equipment

• Inexpensive enzymes, recombinant over-expressed

• More than 95% conversion in 24 hours

• No additional acceptor required

• No expensive ingredients or solvents

• Easy work up and removal of enzyme

• Environmentally friendly

Oxidases

IEPNit Toolbox>15 enzymes

Broad substrate range

25 enzymes

NAD and NADP dependent Formate dehydrogenases (cofactor regeneration NADH and NADPH)

NADP and NAD dependent Glucose dehydrogenases (cofactor regeneration NADH and NADPH)

NADH oxidase

H2OR2

R1 COOR3

R2

R1 COOR3

R1

COOR3

R1

COOH

R2

R1 COOH

R1

COOR3

+

+

O

R OH

OH

O

R OH

OH

O

R OH

O

O2

H2O2

H2O2 O2

IEPLO

R1

OHR1 CHO

+

O

O

HH

H

O

O

HH

H

Androsten-3,17 -dione H2O2 O2

IEPDD

acceptor

acceptor H2

2H2O2 H2O+O2

NAD(P)+ NAD(P)H

+

Formate

H2CO3 H2O CO2

H2O

NAD(P)+GDH NAD(P)H

Glucose

Gluconolactone Gluconic acidH2O

NADH + H+ + O2 NAD + H2O2

IEPNitToolbox> 15 enzymes

Broad substrate range

CNS CN

CN

CN

OHCN

CNN

NOH

NO

CN

CN

H2OR2

R1 COOR3

R2

R1 COOR3

R1

COOR3

R1

COOH

R2

R1 COOH

R1

COOR3

+

+

O

R OH

OH

O

R OH

OH

O

R OH

O

O2

H2O2

H2O2 O2

IEPLO

R1

OHR1 CHO

+

O

O

HH

H

O

O

HH

H

Androsten-3,17 -dione H2O2 O2

IEPDD

acceptor

acceptor H2

2H2O2 H2O+O2

NAD(P)+ NAD(P)H

+

Formate

H2CO3 H2O CO2

H2O

NAD(P)+GDH NAD(P)H

Glucose

Gluconolactone Gluconic acidH2O

NADH + H+ + O2 NAD + H2O2

IEPNitToolbox> 15 enzymes

Broad substrate range

CNS CN

CN

CN

OHCN

CNN

NOH

NO

CN

CN

Peroxidases/Catalases

Contact CambrexExperts you’ll enjoy working withwww.cambrex.com