Enantioselective Biooxidation of Racemic trans‐Cyclic Vicinal Diols: One‐Pot Synthesis of Both Enantiopure (S,S)‐Cyclic Vicinal Diols and (R)‐α‐Hydroxy Ketones

Abstract

Highly regio‐ and enantioselective alcohol dehydrogenases BDHA (2,3‐butanediol dehydrogenase from Bacillus subtilis BGSC1A1), CDDHPm (cyclic diol dehydrogenase from Pseudomonas medocina TA5), and CDDHRh (cyclic diol dehydrogenase from Rhodococcus sp. Moj‐3449) were discovered for the oxidation of racemic trans‐cyclic vicinal diols. Recombinant Escherichia coli expressing BDHA was engineered as an efficient whole‐cell biocatalyst for the oxidation of (±)‐1,2‐cyclopentanediol, 1,2‐cyclohexanediol, 1,2‐cycloheptane‐diol, and 1,2‐cyclooctanediol, respectively, to give the corresponding (R)‐α‐hydroxy ketones in >99% ee and (S,S)‐cyclic diols in >99% ee at 50% conversion in one pot. Escherichia coli (BDHA‐LDH) co‐expressing lactate dehydrogenase (LDH) for intracellular regeneration of NAD+ catalyzed the regio‐ and enantioselective oxidation of (±)‐1,2‐dihydroxy‐1,2,3,4‐tetrahydronaphthalene to produce the corresponding (R)‐α‐hydroxy ketone in >99% ee and (S,S)‐cyclic diol in 96% ee at 49% conversion. Preparative biotransformations were also demonstrated. Thus, a novel and useful method for the one‐pot synthesis of both vicinal diols and α‐hydroxy ketones in high ee was developed via highly regio‐ and enantioselective oxidations of the racemic vicinal diols.magnified image

Arene cis‐Diol Dehydrogenase‐Catalysed Regio‐ and Stereoselective Oxidation of Arene‐, Cycloalkane‐ and Cycloalkene‐cis‐diols to Yield Catechols and Chiral α‐Ketols

“…A recent report convincingly demonstrated the value of bacterial trans‐ diol dehydrogenase enzymes, as biocatalysts for the stereoselective dehydrogenation of cyclic vicinal trans ‐diols and formation of chiral α‐ketols 10e. A complementary study of stereoselectivity, observed during cis ‐diol dehydrogenase‐catalysed dehydrogenation of cyclic vicinal cis ‐diols and formation of chiral α‐ketols, is presented herein.…”

One‐Pot Enzymatic Synthesis of Cyclic Vicinal Diols from Aliphatic Dialdehydes via Intramolecular C−C Bond Formation and Carbonyl Reduction Using Pyruvate Decarboxylases and Alcohol Dehydrogenases

“…The conversion and ee value of 2‐hydroxycyclopentanone ( 2 a ) and 2‐hydroxycyclohexanone ( 2 b ) were determined by GC analysis. The absolute configuration was determined by comparing the relative retention times of the reference (Table S6 in the Supporting Information) …”

“…reported the conversion of cyclohexane, cyclohexanol or cyclohexanone through three steps, two steps or one step to form 2‐hydroxycyclohexanone ( 2 b ) using P450‐BM3 monooxygenase from Bacillus megaterium . Alcohol dehydrogenases BDHA (2,3‐butanediol dehydrogenase from Bacillus subtilis BGSC1 A1) was engineered as an efficient biocatalyst for the stereoselective oxidation of 1,2‐cyclopentanediol ( 3 a ) and 1,2‐cyclohexanediol ( 3 b ) to the corresponding cyclic ( R )‐α‐hydroxy ketones …”

Designer Microorganisms for Optimized Redox Cascade Reactions – Challenges and Future Perspectives

“…[213] After SpEH-mediated epoxide hydrolysis, NAD + + -dependent dehydrogenase oxidizes the diol to the ketone ( Figure 22). Interestingly,t wo different en- Different from the earlier established system using LDH, [214] the whole-cell catalyst was constructed by the co-transformation of pETDuet-1/SpEH-NOX and pET28a/BDHA.A sb oth plasmidss hare the same ORI, plasmid maintenance exclusively relied on the selection by two different antibiotics.T his is in contrast to the concept of plasmid incompatibility and might result in inconsistent expression patterns in different cell populations.…”

“…Different from the earlier established system using LDH,214 the whole‐cell catalyst was constructed by the co‐transformation of pETDuet‐1/ SpEH ‐NOX and pET28a/ BDHA . As both plasmids share the same ORI, plasmid maintenance exclusively relied on the selection by two different antibiotics.…”