Microbial biocatalysis, synthesis

Microbial biocatalysis is often employed for polymer synthesis. A successful application area is the poly(hydroxyalkanoate) (PHA). Thus, Noda et al (22) reported the development of Nodax family of copolymers, which were shown to have versatile physical properties. Srienc et al (23) engineered yeast to produce PHAs comprising 6-13 carbon monomers. Henderson (5) included whole-cell approaches and metabolic engineering in the biomass conversion program. 

The synthesis of oligosaccharides and polysaccharides can also be achieved via microbial biocatalysis. For example, Wang et al (17) devised the Superbug method that could produce oligosaccharides of less than 4 sugar units efficiently. 

Cephalosporins are -lactam antibiotics that block microbial cell wall synthesis. The original cephalosporin. Cephalosporin C, has only weak antibiotic activity. Therefore much more powerful second generation cephalosporins were developed by side-chain modification. Modifications at Cl are most effective but modifications at position 3 are also important so as to increase in vivo activity. Synthesis of the second generation cephalosporin cefuroxime requires the replacement of the C3 acetoxy side-chain of the precursor with a caibamate group. Chemical methods proceed via a hydroxylated intermediate which causes problems due to a tendency to lactonise at low pHs. Therefore development of a biocatalysis step was initiated in order to achieve selective reaction nnder mild conditions. 

For biotechnological synthesis, there is a superb database containing information on miaobial biocatalytic reactions and biodegradation pathways for primarily xenobiotic, chemical componnds. It is called the University of Minnesota Biocatalysis/Biodegradation Database (UM-BBD) at can be fonnd at http //nmbbd.ahc.umn.edu/search/index.html. The goal of the UM-BBD is to provide information on microbial enzyme-catalyzed reactions that are important for biotechnology. 

Johnstone SL, Phillips GT, Robertson BW, Watts PD, Bertola MA, Roger HS, Marx AF (1987) Stereoselective synthesis of S-(-)-/ -blockers via microbially produced epoxide intermediates. In Laane C, Tramper J, Lilly MD (eds) Biocatalysis in organic media. Elsevier, Amsterdam, 387 - 392... 

Azerad R, Buisson D (1992) In Servi S (ed) Microbial Reagents in Organic Synthesis. NATO ASI Series C, vol 381, p. 421, Kluwer, Dordrecht Buisson D, Azerad R, Sanner C, Lacheveque M (1992) Biocatalysis 5 249 Nakamura K, Inoue Y, Matsuda T, Ohno A (1995) Tetrahedron Lett. 36 6263 Fantin G, Fogagnolo M, Giovannini PP, Medici A, Pedrini, P (1995) Tetrahedron Asymmetry 6 3047... 

Abramowicz D (ed) (1990) Biocatalysis, Van Nostrand Reinhold, New York Servi S (ed) (1992) Microbial Reagents in Organic Synthesis, NATO ASI Series C, vol 381, Kluwer Academic Publishers, Dradrecht... 

Biocatalysis is the other option when selectivity (sterio or regio) is a priority in a reaction. The various aspects of biocatalysis are discussed elsewhere in the book the following are some examples of biocatalysts that have been used in important synthesis. Kirner (1995) conducted microbial ring hydroxylation and side chain oxidation of hetero-aromatics (see Fig. 3.18). Such selectivity is difficult to achieve in one step in traditional chemical synthesis. 

Recent developments in o-aminopeptidases, racemases, and oxidases and their application in the synthesis of chiral molecules, microbial transformations of pentacyclic triterpenes, and yeast-mediated enantioselective biocatalysis are described. 

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