Baeyer–Villiger Monooxygenases: Tunable Oxidative Biocatalysts

Abstract

Pollution, accidents, and misinformation have earned the pharmaceutical and chemical industry a poor public reputation, despite their undisputable importance to society. Biotechnological advances hold the promise to enable a future of drastically reduced environmental impact and rigorously more efficient production routes at the same time. This is exemplified in the Baeyer–Villiger reaction, which offers a simple synthetic route to oxidize ketones to esters, but application is hampered by the requirement of hazardous and dangerous reagents. As an attractive alternative, flavin-containing Baeyer–Villiger monooxygenases (BVMOs) have been investigated for their potential as biocatalysts for a long time, and many variants have been characterized. After a general look at the state of biotechnology, we here summarize the literature on biochemical characterizations, mechanistic and structural investigations, as well as enzyme engineering efforts in BVMOs. With a focus on recent developments, we critically outline the advances toward tuning these enzymes suitable for industrial applications.

Genomic scanning enabling discovery of a new antibacterial bicyclic carbamate-containing alkaloid

“…S1A ). GxGxxxG motif has hitherto been used to indicate the presence of FAD which could as readily indicate flavin-monooxygenase-related enzymes [ 22 ]. However, YWWxTKN, and GDAAH motifs, covering approximate 80 amino acid residues, are unique among LgnC-like monooxygenases and as such these two motifs may be used as PCR probe to screen LgnC-like monooxygenase from uncurated genomic DNAs of available bacterial strains ( Table S1 ).…”

Enantioselective sulfoxidation using Streptomyces glaucescens GLA.0

“…The conserved regions are anked by the two Rossmann fold sequence motifs (GXGXX[G/A]). 37 This strongly suggests that this protein is a typical Type I BVMO. The alignment showed that it possesses 86% sequence identity with a BVMO from Streptomyces coelicolor A3(2) (UniProt Accession No.…”

“…22 It was reported that PMSO shows lower biotoxicity compared to PMS which may be due to the hydrophobic nature of the latter as stated before. 22,37,38 Also, phenyl methyl sulfone was reported to be one of the pesticide metabolites that contribute to potential toxicity to soil bacteria. 39 As a result, it is thought to induce the reductase system and undergo deoxygenation once congured.…”

Natural Variation in the ‘Control Loop’ of BVMOAFL210 and Its Influence on Regioselectivity and Sulfoxidation

“…Baeyer-Villiger monooxygenases (BVMOs) are flavin-dependent enzymes that catalyze the conversion of ketones to esters [1,2]. Naturally, they enable the use of alternative carbon sources or the synthesis of various secondary metabolites by microorganisms [3].…”

“…However, their use as alternatives to chemical Baeyer-Villiger catalysts, and their ability to also catalyze heteroatom oxidation, has driven much of the research over the past two decades. This has led the search for new and improved BVMOs to expand on the current substrate-scope, enhanced regio-, enantio-and stereospecificity/selectivity, as well as stability of these promising biocatalysts [1,[4][5][6].…”