title: F420H2-dependent degradation of aflatoxin and other furanocoumarins is widespread throughout the actinomycetales.
abstract: Two classes of F(420)-dependent reductases (FDR-A and FDR-B) that can reduce aflatoxins and thereby degrade them have previously been isolated from Mycobacterium smegmatis. One class, the FDR-A enzymes, has up to 100 times more activity than the other. F(420) is a cofactor with a low reduction potential that is largely confined to the Actinomycetales and some Archaea and Proteobacteria. We have heterologously expressed ten FDR-A enzymes from diverse Actinomycetales, finding that nine can also use F(420)H(2) to reduce aflatoxin. Thus FDR-As may be responsible for the previously observed degradation of aflatoxin in other Actinomycetales. The one FDR-A enzyme that we found not to reduce aflatoxin belonged to a distinct clade (herein denoted FDR-AA), and our subsequent expression and analysis of seven other FDR-AAs from M. smegmatis found that none could reduce aflatoxin. Certain FDR-A and FDR-B enzymes that could reduce aflatoxin also showed activity with coumarin and three furanocoumarins (angelicin, 8-methoxysporalen and imperatorin), but none of the FDR-AAs tested showed any of these activities. The shared feature of the compounds that were substrates was an α,β-unsaturated lactone moiety. This moiety occurs in a wide variety of otherwise recalcitrant xenobiotics and antibiotics, so the FDR-As and FDR-Bs may have evolved to harness the reducing power of F(420) to metabolise such compounds. Mass spectrometry on the products of the FDR-catalyzed reduction of coumarin and the other furanocoumarins shows their spontaneous hydrolysis to multiple products.
authors.affiliation: Ecosystem Sciences, Commonwealth Science and Industrial Research Organisation, Canberra, Australian Capital Territory, Australia.
authors.forename: Gauri V
authors.initials: GV
authors.lastname: Lapalikar
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Taylor
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Warden
authors.forename: Colin
authors.initials: C
authors.lastname: Scott
authors.forename: Robyn J
authors.initials: RJ
authors.lastname: Russell
authors.forename: John G
authors.initials: JG
authors.lastname: Oakeshott
mesh_terms: D000348:Aflatoxins / Q000378:metabolism*; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000737:chemistry; D003374:Coumarins / Q000737:chemistry; D005415:Flavins / Q000737:chemistry; D011564:Furocoumarins / Q000737:chemistry*; D005786:Gene Expression Regulation; D006868:Hydrolysis; D007666:Khellin / Q000737:chemistry; D013058:Mass Spectrometry / Q000379:methods; D008730:Methoxsalen / Q000737:chemistry; D020102:Mycobacterium smegmatis / Q000378:metabolism*; D010088:Oxidoreductases / Q000737:chemistry*; D010802:Phylogeny; D013045:Species Specificity; D015262:Xenobiotics / Q000494:pharmacology
chemical_list: D000348:Aflatoxins; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D003374:Coumarins; D005415:Flavins; D011564:Furocoumarins; D015262:Xenobiotics; D007666:Khellin; C030123:coumarin; C011659:angelicin; C072742:F420H2 dehydrogenase; D010088:Oxidoreductases; C031534:imperatorin; D008730:Methoxsalen