The “Green” FMOs: Diversity, Functionality and Application of Plant Flavoproteins

Abstract

Flavin-dependent monooxygenases (FMOs) are ancient enzymes present in all kingdoms of life. FMOs typically catalyze the incorporation of an oxygen atom from molecular oxygen into small molecules. To date, the majority of functional characterization studies have been performed on mammalian, fungal and bacterial FMOs, showing that they play fundamental roles in drug and xenobiotic metabolism. By contrast, our understanding of FMOs across the plant kingdom is very limited, despite plants possessing far greater FMO diversity compared to both bacteria and other multicellular organisms. Here, we review the progress of plant FMO research, with a focus on FMO diversity and functionality. Significantly, of the FMOs characterized to date, they all perform oxygenation reactions that are crucial steps within hormone metabolism, pathogen resistance, signaling and chemical defense. This demonstrates the fundamental role FMOs have within plant metabolism, and presents significant opportunities for future research pursuits and downstream applications.

A flavin-dependent monooxygenase catalyzes the initial step in cyanogenic glycoside synthesis in ferns

“…Of the limited number of FMOs characterized from plants, only YUCCA6 from A. thaliana and As FMO from garlic ( Allium sativum ) have been successfully expressed and purified in enough quantity for downstream biochemical analyses 33 , 39 , 40 . Here, we expressed the Paq FOS1 protein with an N-terminal 6xHIS tag using Escherichia coli as a heterologous host and isolated Paq FOS1 by immobilized metal affinity chromatography followed by size exclusion chromatography (SEC) with a yield of 0.7 mg/L culture (Fig.…”

“…The four-electron oxidative decarboxylation reaction catalyzed by FOS1 is complex and may impose such a selection pressure. However, FMOs are “loaded guns” with the energy to drive an oxygenation reaction stored in the enzyme without precise docking of the substrate 33 , 39 . This can explain why N -hydroxyphenylalanine escapes the entire enzymatic reaction sequence and is present as an in vivo metabolite in Pa .…”

The Phylogeny of Class B Flavoprotein Monooxygenases and the Origin of the YUCCA Protein Family

“…Are the functions of the YUCCA clade proteins similar to the functions of the plant type IIb FMO proteins, i.e., are the plant or bacterial type IIb FMOs able to transform IPA into auxin? The precise answers to these questions require further comprehensive studies into the biochemical activities of plant type IIb and other FMO proteins [ 31 ].…”

“…YUCCA proteins belong to the flavoprotein monooxygenases superfamily [ 31 ]. The flavoprotein monooxygenases are involved in a wide range of biological processes of living organisms, from catabolism, detoxification, and biosynthesis to the emission of light and control of axons.…”

“…The class of B flavoprotein monooxygenases comprises three subclasses: N -hydroxylating monooxygenases (NMOs), Baeyer–Villiger monooxygenases (BVMOs), and flavin-containing monooxygenases (FMOs) [ 37 ]. The YUCCA family belongs to FMOs [ 31 , 38 ].…”