The recognition of biocatalysts as important manufacturing tool has increased within chemical and pharmaceutical industries in recent years. Biocatalysts can simplify, or in some instances even enable, the production process of complex chemicals and drug intermediates. They can add stereospecificity to the process, eliminating the need for complicated separation and purification steps.

Within the Sigma-Aldrich`s envelope of organic and biochemical capabilities, fermentation has a long tradition with locations in the USA, Israel and Switzerland. At our Fluka facility located at Buchs, Switzerland, a wide range of chemical knowledge is combined with biotechnological expertise. Fluka both develops and produces the biocatalysts on small and large scale, and can subsequently perform the synthesis of the target molecule via biotransformation in-house.

Our newly expanded facility, bioreactors up to 300 lt (2 x 20L, 1 x 75L and 1 x 300L) are currently in operation. All fermentation reactors are completely computer-controlled. The Paragon-Process Control System allows us a continuous 24h-operation with complete documentation of the fermentation or biotransformation process. Process optimization is performed with a miniaturized multifermenter system, which allows simultaneously to follow 6 experiments.

Fermentation process at Fluka is in compliance with ISO-9001/2000. In order to make sure that these standards are applied within reasonable costs we have established new technical systems to facilitate the routine operation. Regular internal and external audits guarantee a constantly high standards of operation. Biosafety is established according to Good Industrial Large Scale Practice (GILSP).

We use both natural and recombinant micro-organisms (bacteria, yeasts and fungi). Recombinant technology allows overexpression of biocatalysts, thereby resulting in higher yields and diminished biological waste. At request of the customer, development and formulation of a custom biocatalyst can take place as well.On the downstream processing side, we apply a wide range of highly qualified technologies, such as bioseparation, expanded bed adsorption, two-phase separation and membrane chromato-graphy. With these technologies the reproducible production of biocatalysts is achieved in highest yields. Table 1 lists examples of our biocatalysts produced in medium to large scale.

In order to fully satisfy the customer`s demands, the production of the biocatalyst can be combined with its direct application in biotransformation. We have experience in routinely performing more than a hundred biocatalytic processes and are ready for large scale production using reactors with total volumes up to 1600L.

The techniques we use on the application side vary widely from simple batch biotransformations over membrane reactors to whole-cell biotrans-formations. Table 2 shows several examples of products we routinely prepare with enzyme catalysts.

For more information about our biocatalysts and biotransformation capabilities please contact www.sigma-aldrich.com/safc or Fluka@sial.com

Table 1. Examples of enzymes produced at medium-large scale at Fluka

Fluka Catalog No.	Product	EC Number	Description
01818	Acylase I	3.5.1.14	from Aspergillus melleus
77038	a-1,3-Galactosyl-Transferase	2.4.1.151	rekombinant from E.coli
48281	Beta-1,4-Galactosyl Transferase	2.4.1.22	from bovine milk
05643	Alcohol Dehydrogenase	1.1.1.2	from Lactobacillus kefir
45299	Epoxy Hydrolase	3.3.2.3	from Rhodococcus rhodochrous
46059	Esterase	3.1.1.1	from Mucor miehei
62299	Lipase	3.1.1.3	from Candida antarctica
81706	Prolidase	3.4.13.9	from Lactococcus lactis
78085	Phenylalanine Deaminase	4.3.1.5	from Rhodotorula glutinis
70797	Alpha-Glucosidase	3.2.1.20	from yeast (Maltase)

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Table 2. Examples of bulk products enzymatically produced at Fluka

Fluka Catalog No.	Product	CAS No.
00850	(1S,4R)-cis-4-acetoxy-2-cyclopenten-1-ol	60410-16-4
07210	D-2-Aminobutyric acid	2623-91-8
09223	(R)-2-Amino-1-phenylethanol	2549-14-6
47352	4-Fluor-L-alpha-phenylglycine	19883-57-9
56112	(R)-2-Hydroxy-4-phenylbutyric acid	29678-81-7
74863	S(+)-2-Octanol	6169-06-8
74865	(R)-(-)-2-Octanol	123-96-6
77848	R(+)-Phenylethanol	1517-69-7
77849	S(-)-Phenylethanol	1445-91-6
78885	(S)-Phenlyoxirane	20780-54-5

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