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Stereoselective oxidation of aryl-substituted vicinal diols into chiral α-hydroxy aldehydes by re-engineered propanediol oxidoreductase
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Biochemistry.
Åbo Akademi.
Åbo Akademi.
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Biochemistry.
2013 (English)In: ACS Catalysis, ISSN 2155-5435, Vol. 3, no 12, 3016-3025 p.Article in journal (Refereed) Published
Abstract [en]

α-Hydroxy aldehydes are chiral building blocks used in synthesis of natural products and synthetic drugs. One route to their production is by regioselective oxidation of vicinal diols and, in this work, we aimed to perform the oxidation of 3-phenyl-1,2-propanediol into the corresponding α‑hydroxy aldehyde applying enzyme catalysis. Propanediol oxidoreductase from E. coli efficiently catalyzes the stereoselective oxidation of S-1,2-propanediol into S-lactaldehyde. The enzyme, however, shows no detectable activity with aryl-substituted or other bulky alcohols. We conducted ISM-driven directed evolution on FucO and were able to isolate several mutants that were active with S-3-phenyl-1,2-propanediol. The most efficient variant displayed a kcat/KM of 40 s-1M-1 and the most enantioselective variant an E-value (S/R) of 80. Furthermore, other isolated variants showed up to 4400-fold increased activity with another bulky substrate, phenylacetaldehyde. The results with engineered propanediol oxidoreductases identified amino acids important for substrate selectivity and asymmetric synthesis of aryl-substituted α-hydroxy aldehydes. In conclusion, our study demonstrates the feasibility of tailoring the catalytic properties of propanediol oxidoreductase for biocatalytic properties.

Place, publisher, year, edition, pages
2013. Vol. 3, no 12, 3016-3025 p.
Keyword [en]
biocatalytic diol oxidation, regioselectivity, directed enzyme evolution, principal components analysis, steady-state kinetics
National Category
Biochemistry and Molecular Biology
Research subject
Biochemistry
Identifiers
URN: urn:nbn:se:uu:diva-210303DOI: 10.1021/cs400824hISI: 000328231400041OAI: oai:DiVA.org:uu-210303DiVA: diva2:661932
Available from: 2013-11-05 Created: 2013-11-05 Last updated: 2014-01-13Bibliographically approved

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Blikstad, CeciliaWidersten, Mikael

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