F420H2-dependent degradation of aflatoxin and other furanocoumarins is widespread throughout the Actinomycetales

Gauri V. Lapalikar, Matthew C. Taylor, Andrew C. Warden, Colin Scott, Robyn J. Russell, John G. Oakeshott

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31 Citations (Scopus)

Abstract

Two classes of F420-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. F420 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 F420H2 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 F420 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.

Original languageEnglish
Article numbere30114
Pages (from-to)1-9
Number of pages9
JournalPLoS ONE
Volume7
Issue number2
DOIs
Publication statusPublished - 27 Feb 2012
Externally publishedYes

Bibliographical note

Copyright Lapalikar et al. 2012. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

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    Lapalikar, G. V., Taylor, M. C., Warden, A. C., Scott, C., Russell, R. J., & Oakeshott, J. G. (2012). F420H2-dependent degradation of aflatoxin and other furanocoumarins is widespread throughout the Actinomycetales. PLoS ONE, 7(2), 1-9. [e30114]. https://doi.org/10.1371/journal.pone.0030114