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Polycyclic Ketone Monooxygenase from the Thermophilic Fungus Thermothelomyces thermophila: A Structurally Distinct Biocatalyst for Bulky Substrates

Regio- and stereoselective Baeyer–Villiger oxidations are difficult to achieve by classical chemical means, particularly when large, functionalized molecules are to be converted. Biocatalysis using flavin-containing Baeyer–Villiger monooxygenases (BVMOs) is a well-established tool to address these c...

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Published in:Journal of the American Chemical Society 2017-01, Vol.139 (2), p.627-630
Main Authors: Fürst, Maximilian J. L. J, Savino, Simone, Dudek, Hanna M, Gómez Castellanos, J. Rúben, Gutiérrez de Souza, Cora, Rovida, Stefano, Fraaije, Marco W, Mattevi, Andrea
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cited_by cdi_FETCH-LOGICAL-a399t-f38f29915b3a86c8ade405f922e0dfa10ca6ff70cea45a5a6dedd0379fad040b3
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container_title Journal of the American Chemical Society
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creator Fürst, Maximilian J. L. J
Savino, Simone
Dudek, Hanna M
Gómez Castellanos, J. Rúben
Gutiérrez de Souza, Cora
Rovida, Stefano
Fraaije, Marco W
Mattevi, Andrea
description Regio- and stereoselective Baeyer–Villiger oxidations are difficult to achieve by classical chemical means, particularly when large, functionalized molecules are to be converted. Biocatalysis using flavin-containing Baeyer–Villiger monooxygenases (BVMOs) is a well-established tool to address these challenges, but known BVMOs have shortcomings in either stability or substrate selectivity. We characterized a novel BVMO from the thermophilic fungus Thermothelomyces thermophila, determined its three-dimensional structure, and demonstrated its use as a promising biocatalyst. This fungal enzyme displays excellent enantioselectivity, acts on various ketones, and is particularly active on polycyclic molecules. Most notably we observed that the enzyme can perform oxidations on both the A and D ring when converting steroids. These functional properties can be linked to unique structural features, which identify enzymes acting on bulky substrates as a distinct subgroup of the BVMO class.
doi_str_mv 10.1021/jacs.6b12246
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source American Chemical Society:Jisc Collections:American Chemical Society Read & Publish Agreement 2022-2024 (Reading list)
subjects Cyclization
Fungi - enzymology
Ketones - chemistry
Mixed Function Oxygenases - chemistry
Stereoisomerism
title Polycyclic Ketone Monooxygenase from the Thermophilic Fungus Thermothelomyces thermophila: A Structurally Distinct Biocatalyst for Bulky Substrates
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