Small Molecules

Enzyme Classes

DowpharmaSM has collections of commercial enzymes, in-house cloned enzymes and clone banks as well as a microbial collection of over 2,000 strains. We have industry-leading experience in the discovery and use of hydrolase enzymes — the most versatile and industrially proven enzymes to date.

Choose an enzyme class:

Lipases/Esterases
Lipases/esterases are highly advantaged enzymes for the preparation of carboxylic esters, acids, alcohols and amines:

  • More than 400 enzymes available to screen
  • Fast screening and direct scale up — no specialist equipment required
  • Wide substrate specificities
  • High stereoselectivity and regioselectivity
  • Versatility — can be used in aqueous or organic solvents
  • Robust catalysts
  • Lower cost and less waste due to high substrate concentrations and mild reaction conditions

The example below shows the preparation of (S)-β-phenylalanine using a lipase catalysed hydrolytic resolution of the ethyl ester — 200g/l ethyl ester substrate in aqueous buffer. This process has been quickly and easily scaled up to 100s kilogram scale.

Lipases/Esterases

Acylases
These enzymes are primarily used for the preparation of α-amino acids.

  • A collection of commercial and in-house D- and L-acylases available
  • Wide substrate specificity
  • High stereoselectivity
  • Lower cost and less waste due to high substrate concentrations and mild reaction conditions
  • Can be used as resolution catalysts or in conjunction with asymmetric hydrogenation as mild deprotection catalysts.
  • Fast scale up — no specialist equipment required

Example: The thermophilic properties of our in-house L-Acylase allowed the large-scale resolution of a customer product (>100 kg made). In this case the poor substrate solubility meant the reaction was too slow at room temperature and hence not viable. By using our enzyme at 70°C, the solubility of the substrate was significantly increased and the reaction proceeded at a fast rate. Commercial acylase was inactive at this temperature.

Acylases

Acylases

For more information, see:
Biocatalysis – Use of a Thermophilic L-Acylase for the Manufacture of Unusual α-Amino Acids (149KB PDF)


Nitrilases
Another versatile class of enzymes used to make chiral carboxylic acids and nitriles, nitrilases catalyze the hydrolysis of organonitrile compounds to the corresponding carboxylic acids under mild conditions. We offer you:

  • A collection of more than 100 nitrilases available to screen
  • Both (S)- and (R)-selective enzymes are available
  • Wide substrate specificities
  • High enantio-, chemo-, and regioselectivities
  • Conventional and dynamic resolutions possible

Nitrilases

For more information, see:
Biocatalysis – Production of Chiral Carboxylic Acids using Nitrilases (172KB PDF)


Alcohol Dehydrogenases
Secondary alcohols are key chiral building blocks in both the pharmaceutical and fine chemicals industriesy.industry. Alcohol dehydrogenase (ADH) enzymes offer an efficient means to synthesise enantiomerically pure secondary alcohols in high yields.

ADH enzymes offer the following benefits:

  • Asymmetric reaction – theoretical 100% yield of desired isomer
  • Accept a wide variety of substrates
  • (R)- and (S)- specific ADH enzymes available
  • High substrate concentrations possible
  • Mild reaction conditions

Dowpharma can access your target compound through:

  • High throughput screening of ADH enzymes
  • Effective in-house ADH culture collection
  • Capability to discover new ADH enzymes
  • Off the shelf ADH enzymes for rapid process development
  • Ability to compare our range of chemocatalysts and biocatalysts to provide the best manufacturing solution.

Alcohol Dehydrogenases


Secondary Amidases
Secondary amines are key chiral building blocks in both the pharmaceutical and fine chemicals industries. Dowpharma has access to a variety of complementary chiral technologies that allow us to efficiently synthesise enantiomerically pure amines in high yields. As part of this offering we have a collection of 80 secondary amidases for the kinetic resolution of secondary amines.

Nitrilases

  • Diverse array of structures accepted as substrates - aliphatic; aromatic
  • (R)- and (S)-selective enzymes available
  • These enzymes can also be used as mild deprotection agents in conjunction with asymmetric hydrogenation of acyl enamides for 100% theoretical yield of desired enantiomer
  • Enzymes can also be used for reverse reaction – amide synthesis.

Nitrilases


Culture Collection
Enzyme activities accessible through our culture collection

Our culture collection of 2000 strains is available for screening for any desired enzyme activity. For example:

  • Alcohol dehydrogenases for the preparation of secondary alcohols in 100% yield from ketones
  • Aldolases for the preparation of polyhydroxy intermediates
  • Amidases for the preparation of amines

Once the desired enzyme activity has been identified, we can clone out and over-express that desired activity. Cloned enzymes give rise to lower cost catalysts with improved performance. Example: Development of a γ-lactamase to prepare (-)-lactam

  • No bioresolution was known.
  • We performed a microbial screen and identified a hit.
  • We cloned the enzyme activity to produce low cost cloned lactamase.
  • The process was simple and efficient – bioresolution run at 500g/l substrate and product recovered by a direct solvent extraction.
  • Multi-tonnes product was made.


Culture Collection

For more information, please see the following paper published in Chimica Oggi.
Use of lactamases for industrial scale preparation of Chiral Synthons for pharmaceutical research (207KB PDF)

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