Flavoenzymes: Versatile catalysts in biosynthetic pathways

Abstract

Riboflavin-based coenzymes, tightly bound to enzymes catalyzing substrate oxidations and reductions, enable an enormous range of chemical transformations in biosynthetic pathways. Flavoenzymes catalyze substrate oxidations involving amine and alcohol oxidations and desaturations to olefins, the latter setting up Diels-Alder cyclizations in lovastatin and solanapyrone biosyntheses. Both C4a and N5 of the flavin coenzymes are sites for covalent adduct formation. For example, the reactivity of dihydroflavins with molecular oxygen leads to flavin-4a-OOH adducts which then carry out a diverse range of oxygen transfers, including Baeyer-Villiger type ring expansions, olefin epoxidations, halogenations via transient HOCl generation, and an oxidative Favorskii rerrangement during enterocin assembly.

Plasticity, dynamics, and inhibition of emerging tetracycline resistance enzymes

“…Growing evidence, however, indicates that enzymatic tetracycline inactivation is a widespread feature in soil microbial communities 28 , and is a recently observed emerging threat in human pathogens 46-48 . Flavoenzymes display a proclivity for horizontal gene transfer and gene duplication, bestowing the potential to spread between bacteria and acquire novel functions 49 . Interestingly, the contigs on which tet (47-55) were discovered also contained mobility elements and other resistance genes 9,28 ,suggesting that their original genomic context may be as part of a multidrug resistance cassette or mobile genetic element.…”

Functional assembly of camphor converting two-component Baeyer–Villiger monooxygenases with a flavin reductase from E. coli

“…This is advantageous compared to traditional chemical processes that are using environmentally harmful peracids (recent reviews: Balke et al 2012;Leisch et al 2011). The relevant enzymes, termed BaeyerVilliger monooxygenases (BVMOs), are members of a superfamily of flavoprotein monooxygenases mechanistically related by their ability to activate molecular oxygen by generation of a covalent adduct with flavin adenine dinucleotide (FAD) or flavin mononucleotide (FMN) (Harayama et al 1992;Massey 1994;Walsh and Wencewicz 2013).…”

Terminal Alkenes from Acrylic Acid Derivatives via Non‐Oxidative Enzymatic Decarboxylation by Ferulic Acid Decarboxylases

“…FDC‐catalysed decarboxylation of cinnamic acid derivatives mediated by prFMN is proposed to proceed via a 1,3‐dipolar cycloaddition,27,28 in which prFMN acts as 1,3‐dipolar diene owing to its azomethine ylide character 28,33, 34, 35. While this type of transformation – commonly referred to as ′Huisgen‐reaction′36,37 – is widely utilised in heterocyclic synthesis, enzymatic equivalents to this reaction are rare 38, 39, 40, 41…”