Microbial bioreductions

It may also be possible to stimulate bioreductions in soils, such as Cr(VI) to Cr(III), more effectively by growing plants than by adding bacteria or nutrients to stimulate the microbial process. 

Nitrofurantoin, a anti-microbial agent under investigation for use in cancer therapy, also undergoes bioreduction to a nitro radical anion. Following earlier, contradictory reports, Miller et al. have re-examined the possibility that NF can oxidise GSH. Using three different methods of NF generation, the authors found no evidence for reaction between GSH and the radical.127... 

Bottlenecks for bioreduction of prochiral carbonyl compounds by microbial cells for industrial use production... 

Bottlenecks for Bioreduction of Prochiral Carbonyl Compounds by Microbial Cells for Industrial Use Production of (fl)-4-Chloro-3-Hydroxybutanoate Ethyl Ester... 

What are the bottelnecks for bioreduction The drawbacks of a bioreduction process involving whole cells of microoganisms can be summarized i) Microbial strains possessing both carbonyl reductase activity and cofactor (NAD(P)H)-regenerating activity are necessary to obtain a highmolar yield, because a stoichiometric amount of cofactor is required for substrate reduc-... 

This bioreduction system is applicable to the production of many other useful chiral alcohols by replacing the carbonyl reductase gene with that of another appropriate enzyme for carbonyl reduction (Fig. 19.6). A good library of microbial carbonyl reductases with different substrate and stereospecifici-... 

Although reductases play an important role in the in vivo synthesis of many chemicals (see flavour example in Fig. 7.11), little attention has been paid to this type of biocatalyst. In most cases whole microbial or plant cells are used to perform a bioreductive reaction due to the requirement for (expensive) cofactors. Typical examples include the reduction of certain double bonds in terpenes by plant cells [27,41], the reduction of Massoi lactone to R(+)-8-decalactone by Basidiomycetes and S. cerevisiae [28], and the baker s yeast-catalyzed reduction of ketones to (chiral) alcohols [42]. 

In cases where steady-state conditions are achieved, Donnan dialysis can be effectively integrated with Hg(II) bioreduction to Hg(0) using mixed microbial cultures. While many organisms have been shown to perform Hg(II) bioreduction in pure culture, mixed microbial cultures offer the advantage of not requiring aseptic operational conditions, and can thus be much more readily integrated with the lEMB process, where aseptic conditions would involve additional operational costs and complicate the process unnecessarily. Efficient Hg(II) bioreducing mixed cultures have... 

In most of these bioreductions, the ds-(3f, 41 )-hydroxy ester 19a was the major isolated product with high enantioselectivity (98.2-99.8% ee) and diastereoselectivity (97.4-99.5% de) (Scheme 12.10). This specific compound is a useful intermediate for the synthesis of many pharmaceuticals. Moreover, even in larpr scale experiments, the microbial reduction of 19 proceeds in high yields and with good stereoselectivities. In previous reports (14c], the baker s yeast reduction of this substrate gave the same cis-(3R,4R)-hydroxy ester with much lower diastereoselectivity (73% de), thus requiring extended separation steps in order to increase the de and ee values to a level required for further synthetic purposes by the pharmaceutical industry. 

Figure 13.5 (a) Asymmetric bioreduction to chiral alcohol as key intermediate in ezetimibe synthesis, (b) Microbial reduction of ezetimibe precursor to bioactive form of ezetimibe. 

Prior to the widespread awdlabdity of recombiant carbonyl reductases enzymes, the use of microbial reductions using either actively growing or dormant cells was commonplace Bakers yeast in particular, was a readily available source of stereoselective carbonyl reductases enzymes. Even with the widespread knowledge of the power of recombinant CRED biocatalysts, the literature is still rife with wild-type whole-cell microbial reductions. The reductions presented have advanced well beyond the early Bakers yeast reduction and have an apphcation even today. When the whole-cell fermentation is developed and finely tuned, high titers of product alcohol are possible and Scheme 6.4 shows m example of a keto-amide 12 bioreduction performing at 100 g/L with more than 98% ee with multi-kg isolation [12]. The bioprocess was performed over 8 days at pH 7 using the yeast Candida sorbophila. 

The bioreduction of nitroaromatic compounds can proceed with the formation of the intermediary nitroso and hydroxylamine metabolites. That the fates of these intermediates in a microbial milieu are potentially numerous should be evident from this presentation of their chemical properties. Much of this information originated from research on the mechanisms by which arylhydroxylamine and nitrosoarene compounds cause toxicity in higher organisms. Covalent binding of these intermediates to cellular macromolecules can occur either directly in the case of nitrosoarene compounds and proteins, or indirectly in the case... 

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