PMID- 32286819 OWN - NLM STAT- MEDLINE DCOM- 20210413 LR - 20210413 IS - 1520-5126 (Electronic) IS - 0002-7863 (Linking) VI - 142 IP - 18 DP - 2020 May 6 TI - Biphasic Bioelectrocatalytic Synthesis of Chiral beta-Hydroxy Nitriles. PG - 8374-8382 LID - 10.1021/jacs.0c01890 [doi] AB - Two obstacles limit the application of oxidoreductase-based asymmetric synthesis. One is the consumption of high stoichiometric amounts of reduced cofactor. The other is the low solubility of organic substrates, intermediates, and products in the aqueous phase. In order to address these two obstacles to oxidoreductase-based asymmetric synthesis, a biphasic bioelectrocatalytic system was constructed and applied. In this study, the preparation of chiral beta-hydroxy nitriles catalyzed by alcohol dehydrogenase (AdhS) and halohydrin dehalogenase (HHDH) was investigated as a model bioelectrosynthesis, since they are high-value intermediates in statin synthesis. Diaphorase (DH) was immobilized by a cobaltocene-modified poly(allylamine) redox polymer on the electrode surface (DH/Cc-PAA bioelectrode) to achieve effective bioelectrocatalytic NADH regeneration. Since AdhS is a NAD-dependent dehydrogenase, the diaphorase-modified biocathode was used to regenerate NADH to support the conversion from ethyl 4-chloroacetoacetate (COBE) to ethyl (S)-4-chloro-3-hydroxybutanoate ((S)-CHBE) catalyzed by AdhS. The addition of methyl tert-butyl ether (MTBE) as an organic phase not only increased the uploading of COBE but also prevented the spontaneous hydrolysis of COBE, extended the lifetime of DH/Cc-PAA bioelectrode, and increased the Faradaic efficiency and the concentration of generated (R)-ethyl-4-cyano-3-hydroxybutyrate ((R)-CHCN). After 10 h of reaction, the highest concentration of (R)-CHCN in the biphasic bioelectrocatalytic system was 25.5 mM with 81.2% enantiomeric excess (ee(p)). The conversion ratio of COBE achieved 85%, which was 8.8 times higher than that achieved with the single-phase system. Besides COBE, two other substrates with aromatic ring structures were also used in this biphasic bioelectrocatalytic system to prepare the corresponding chiral beta-hydroxy nitriles. The results indicate that the biphasic bioelectrocatalytic system has the potential to produce a variety of beta-hydroxy nitriles with different structures. FAU - Dong, Fangyuan AU - Dong F AUID- ORCID: 0000-0002-1530-8230 AD - Department of Chemistry, University of Utah, 315 South 1400 East, RM 2020, Salt Lake City, Utah 84112, United States. FAU - Chen, Hui AU - Chen H AUID- ORCID: 0000-0002-8944-0090 AD - Department of Chemistry, University of Utah, 315 South 1400 East, RM 2020, Salt Lake City, Utah 84112, United States. FAU - Malapit, Christian A AU - Malapit CA AUID- ORCID: 0000-0002-8471-4208 AD - Department of Chemistry, University of Utah, 315 South 1400 East, RM 2020, Salt Lake City, Utah 84112, United States. FAU - Prater, Matthew B AU - Prater MB AD - Department of Chemistry, University of Utah, 315 South 1400 East, RM 2020, Salt Lake City, Utah 84112, United States. FAU - Li, Min AU - Li M AD - Department of Chemistry, University of Utah, 315 South 1400 East, RM 2020, Salt Lake City, Utah 84112, United States. FAU - Yuan, Mengwei AU - Yuan M AD - Department of Chemistry, University of Utah, 315 South 1400 East, RM 2020, Salt Lake City, Utah 84112, United States. FAU - Lim, Koun AU - Lim K AD - Department of Chemistry, University of Utah, 315 South 1400 East, RM 2020, Salt Lake City, Utah 84112, United States. FAU - Minteer, Shelley D AU - Minteer SD AUID- ORCID: 0000-0002-5788-2249 AD - Department of Chemistry, University of Utah, 315 South 1400 East, RM 2020, Salt Lake City, Utah 84112, United States. LA - eng PT - Journal Article PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20200427 PL - United States TA - J Am Chem Soc JT - Journal of the American Chemical Society JID - 7503056 RN - 0 (Nitriles) RN - EC 1.1.1.1 (Alcohol Dehydrogenase) RN - EC 3.- (Hydrolases) RN - EC 3.8.1.- (halohydrin dehalogenase) SB - IM MH - Alcohol Dehydrogenase/chemistry/*metabolism MH - Biocatalysis MH - Electrochemical Techniques MH - Hydrolases/chemistry/*metabolism MH - Molecular Structure MH - Nitriles/chemistry/*metabolism EDAT- 2020/04/15 06:00 MHDA- 2021/04/14 06:00 CRDT- 2020/04/15 06:00 PHST- 2020/04/15 06:00 [pubmed] PHST- 2021/04/14 06:00 [medline] PHST- 2020/04/15 06:00 [entrez] AID - 10.1021/jacs.0c01890 [doi] PST - ppublish SO - J Am Chem Soc. 2020 May 6;142(18):8374-8382. doi: 10.1021/jacs.0c01890. Epub 2020 Apr 27.