Structural basis for a highly (S)-enantioselective reductase towards aliphatic ketones with only one carbon difference between side chain.

Autor: Koesoema AA; Department of Life Science and Technology, School of Life Science and Technology, Tokyo Institute of Technology, 4259 Nagatsuta-cho Midori-ku, Yokohama, 226-8501, Japan., Sugiyama Y; Department of Life Science and Technology, School of Life Science and Technology, Tokyo Institute of Technology, 4259 Nagatsuta-cho Midori-ku, Yokohama, 226-8501, Japan., Xu Z; Department of Genome Informatics, Genome Information Research Center, Research Institute of Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka, 565-0871, Japan., Standley DM; Department of Genome Informatics, Genome Information Research Center, Research Institute of Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka, 565-0871, Japan. standley@biken.osaka-u.ac.jp., Senda M; Structural Biology Research Center, Institute of Materials Structure Science, High Energy Accelerator Research Organization (KEK), 1-1 Oho Tsukuba, Ibaraki, 305-0801, Japan., Senda T; Structural Biology Research Center, Institute of Materials Structure Science, High Energy Accelerator Research Organization (KEK), 1-1 Oho Tsukuba, Ibaraki, 305-0801, Japan. toshiya.senda@kek.jp.; Department of Materials Structure Science, School of High Energy Accelerator Science, SOKENDAI (The Graduate University for Advanced Studies), 1-1 Oho, Tsukuba, Ibaraki, 305-0801, Japan. toshiya.senda@kek.jp., Matsuda T; Department of Life Science and Technology, School of Life Science and Technology, Tokyo Institute of Technology, 4259 Nagatsuta-cho Midori-ku, Yokohama, 226-8501, Japan. tmatsuda@bio.titech.ac.jp.
Jazyk: angličtina
Zdroj: Applied microbiology and biotechnology [Appl Microbiol Biotechnol] 2019 Dec; Vol. 103 (23-24), pp. 9543-9553. Date of Electronic Publication: 2019 Nov 15.
DOI: 10.1007/s00253-019-10093-w
Abstrakt: Aliphatic ketones, such as 2-butanone and 3-hexanone, with only one carbon difference among side chains adjacent to the carbonyl carbon are difficult to be reduced enantioselectively. In this study, we utilized an acetophenone reductase from Geotrichum candidum NBRC 4597 (GcAPRD) to reduce challenging aliphatic ketones such as 2-butanone (methyl ethyl ketone) and 3-hexanone (ethyl propyl ketone) to their corresponding (S)-alcohols with 94% ee and > 99% ee, respectively. Through crystallographic structure determination, it was suggested that residue Trp288 limit the size of the small binding pocket. Docking simulations imply that Trp288 plays an important role to form a C-H⋯π interaction for proper orientation of ketones in the pro-S binding pose in order to produce (S)-alcohols. The excellent (S)-enantioselectivity is due to a non-productive pro-R binding pose, consistent with the observation that the (R)-alcohol acts as an inhibitor of (S)-alcohol oxidation.
Databáze: MEDLINE
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