Enantiomeric whole-cell processes

Biocatalysts these are essential for life and play a vital role in most processes occurring within the body as well as in plants. In the laboratory biocatalysts are usually natural enzymes or enzymes produced in situ from whole cells. They offer the possibility of carrying out many difficult transformations under mild conditions and are especially valuable for producing enantiomerically pure materials. Their huge potential is currently largely untapped, partially due to the time and expense of isolating and screening enzymes. 

All biotechnological processes depend on enzymes - either in whole-cell living systems or isolated out of their biological context. In fact, purified enzymes are established in processing food and textiles and are supplements in feed and detergents - all products of everybody s daily life. Whole-cell systems particularly in the field of specialty chemicals provide a broad range of methods and processes. For many years, enantiomerically pure amino acids for food, feed and pharma industries have been produced by microbial fermentation. Ambitious R D resulted in enzymes especially modified and optimized for a desired chemical reaction such as biocatalysis of optically active amines, alcohols, epoxides and more. ... 

This process only becomes possible when both enantiomers are converted by two independent enantioselective reactions to the same enantiomeric product. Both pathways must exhibit an opposite sense of enantioselectivity. For example, as shown in Scheme 5.58, whole-cell microbial transformation of a racemic epoxide using two different organisms, each harbouring a hydrolase that performs the enantioselective hydrolysis of the epoxide ring (with opposite stereocontrol), to give a single enantiomeric 1,2-diol as the sole product in high yield with excellent enantiomeric excess [148]. 

Recently, this strategy was applied to the deracemization of propargylic alcohols that are important synthons for the preparation of biologically active compounds such as mifepristone, efavirenz, or petrosynol [63]. A one-pot two-step process employing whole cells from Candida parapsilosis ATCC 7330 was carried out in aqueous medium using short reaction times of 1—4h (Scheme 4.15). Biocatalyzed transformations afforded excellent enantiomeric excess (up to 99%) and isolated yields were from 60-81%. 

Asymmetric reductions with enzymes from diverse sources have shown a great potential in successful DKR processes. The use of whole cells of microorganisms in DKR has been shown to provide alternative way when cofactors regeneration is required. The development of new biocatalysts has been greatly promoted from the utilization of enzymes expressed and the increased availability of genes in data bank. The increased number of commercially available oxidoreductases has also contributed a lot to the progress of asymmetric synthesis toward enantiomerically pure bioactive compounds. 

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