Bioreduction using CRED

Acetophenone-type compounds dominate in the literature and are a successful class of compounds for bioreductions using CRED enzymes. Their simple availability, minimal steric hindrance around the ketone, and excellent solubility in a range of solvents make them useful substrates for further study. 

Concurrent biooxidation and bioreduction using CRED technology. 

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 key challenges with this dass of compound come from steric hindrance around the ketone moiety, poor solubility under aqueous conditions, and (often) lack of acceptance by CRED enzymes. Fortunately, more and more enzymes are being identified and evolved in order to tolerate such substrates. The montelukast bioreduction shown earlier in Scheme 6.2 elegantly demonstrates how CREDs can be evolved to accept bulky ketones. Tmppo et al. at Merck showed that a series of benzophenones 61 could be selectivdy reduced using commerdally available... 

---