Controlling the Regioselectivity of Baeyer-Villiger Monooxygenases by Mutation of Active-Site Residues

Chembiochem : a European Journal of Chemical Biology
Kathleen BalkeUwe T Bornscheuer

Abstract

Baeyer-Villiger monooxygenase (BVMO)-mediated regiodivergent conversions of asymmetric ketones can lead to the formation of "normal" or "abnormal" lactones. In a previous study, we were able to change the regioselectivity of a BVMO by mutation of the active-site residues to smaller amino acids, which thus created more space. In this study, we demonstrate that this method can also be used for other BVMO/substrate combinations. We investigated the regioselectivity of 2-oxo-Δ3 -4,5,5-trimethylcyclopentenylacetyl-CoA monooxygenase from Pseudomonas putida (OTEMO) for cis-bicyclo[3.2.0]hept-2-en-6-one (1) and trans-dihydrocarvone (2), and we were able to switch the regioselectivity of this enzyme for one of the substrate enantiomers. The OTEMO wild-type enzyme converted (-)-1 into an equal (50:50) mixture of the normal and abnormal products. The F255A/F443V variant produced 90 % of the normal product, whereas the W501V variant formed up to 98 % of the abnormal product. OTEMO F255A exclusively produced the normal lactone from (+)-2, whereas the wild-type enzyme was selective for the production of the abnormal product. The positions of these amino acids were equivalent to those mutated in the cyclohexanone monooxygenases from Arthrobac...Continue Reading

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Citations

Mar 25, 2018·Angewandte Chemie·JiaJia DongWuyuan Zhang
Jul 20, 2018·Chembiochem : a European Journal of Chemical Biology·Jia-Mei YuJian-He Xu
Nov 16, 2018·Chembiochem : a European Journal of Chemical Biology·Gabriel A Ascue AvalosNigel S Scrutton
Mar 31, 2019·Applied and Environmental Microbiology·Yuan-Yang LiuGao-Wei Zheng
Feb 23, 2019·Chembiochem : a European Journal of Chemical Biology·Arne StammPer-Olof Syrén
Oct 28, 2017·Chembiochem : a European Journal of Chemical Biology·Marie A F DelgoveStefaan M A De Wildeman
Nov 19, 2020·Chembiochem : a European Journal of Chemical Biology·Guang-Xiang ZhangChun-Xiu Li
Dec 17, 2020·Chemical Society Reviews·Sjoerd Slagman, Wolf-Dieter Fessner
Feb 10, 2021·International Journal of Molecular Sciences·Constantin TănaseRaluca Elena Tănase
Jan 29, 2019·ACS Catalysis·Maximilian J L J FürstAndrea Mattevi
Jan 13, 2018·Chemical Reviews·Elvira RomeroAndrea Mattevi
Mar 14, 2018·Biochemistry·Hanan L MessihaNigel S Scrutton

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