Baeyer–Villiger Monooxygenases (BVMOs) as Biocatalysts

Abstract

Natural or artificial enzymes are used in biocatalytic processes to produce high-value fine chemicals, most notably chiral pharmaceutical intermediates. On the other hand, there are few instances of the enzymatic production of bulk compounds.1 In particular production of polymer precursors such as -caprolactone, currently obtained from cyclohexanone utilizing peracetic acid; where Baeyer–Villiger monooxygenases (BVMOs) are potential alternative catalysts to carry out the reaction under much milder conditions.2 Bulk manufacturing of feedstock chemicals utilizing biocatalysts such as BVMO has yet to be accomplished due to a number of reasons.3 The versatility of BVMOs is highlighted in this Spotlight, along with various instances of how protein engineering has been employed to circumvent some of the disadvantages of BVMO use. BVMOs are flavin-reliant enzymes that utilize molecular oxygen and NAD(P)H to catalyze a number of oxidation processes, including Baeyer–Villiger oxidations (Table 1).4,5 The genes to encode them were discovered at the beginning of this century.6 Even though the biochemical reason for the retention of these residues was unclear until recently, the sequence pattern has shown to be quite useful for mining genomes for new BVMOs.7 Although the genomes of higher animals and plants do not include any type I BVMOs, bacteria are rich in BVMOs, with one BVMO per genome on average.8 These enzymes are notably common among the Actinomycetes, making them an intriguing source of new BVMOs.9 Fungal genomes are also rather rich in BVMOs but have not yet been fully investigated.10 The crucial functions that BVMOs play in microbial metabolic pathways have recently been confirmed by investigations on the biotransformation of natural compounds.11–13