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

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 poten...

Full description

Bibliographic Details
Main Authors: Gauri V Lapalikar, Matthew C Taylor, Andrew C Warden, Colin Scott, Robyn J Russell, John G Oakeshott
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2012-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3288000?pdf=render
_version_ 1818316062788157440
author Gauri V Lapalikar
Matthew C Taylor
Andrew C Warden
Colin Scott
Robyn J Russell
John G Oakeshott
author_facet Gauri V Lapalikar
Matthew C Taylor
Andrew C Warden
Colin Scott
Robyn J Russell
John G Oakeshott
author_sort Gauri V Lapalikar
collection DOAJ
description 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.
first_indexed 2024-12-13T09:15:28Z
format Article
id doaj.art-06358edfb8334964a2b5d9f0fbc2ed11
institution Directory Open Access Journal
issn 1932-6203
language English
last_indexed 2024-12-13T09:15:28Z
publishDate 2012-01-01
publisher Public Library of Science (PLoS)
record_format Article
series PLoS ONE
spelling doaj.art-06358edfb8334964a2b5d9f0fbc2ed112022-12-21T23:52:50ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0172e3011410.1371/journal.pone.0030114F420H2-dependent degradation of aflatoxin and other furanocoumarins is widespread throughout the actinomycetales.Gauri V LapalikarMatthew C TaylorAndrew C WardenColin ScottRobyn J RussellJohn G OakeshottTwo 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.http://europepmc.org/articles/PMC3288000?pdf=render
spellingShingle Gauri V Lapalikar
Matthew C Taylor
Andrew C Warden
Colin Scott
Robyn J Russell
John G Oakeshott
F420H2-dependent degradation of aflatoxin and other furanocoumarins is widespread throughout the actinomycetales.
PLoS ONE
title F420H2-dependent degradation of aflatoxin and other furanocoumarins is widespread throughout the actinomycetales.
title_full F420H2-dependent degradation of aflatoxin and other furanocoumarins is widespread throughout the actinomycetales.
title_fullStr F420H2-dependent degradation of aflatoxin and other furanocoumarins is widespread throughout the actinomycetales.
title_full_unstemmed F420H2-dependent degradation of aflatoxin and other furanocoumarins is widespread throughout the actinomycetales.
title_short F420H2-dependent degradation of aflatoxin and other furanocoumarins is widespread throughout the actinomycetales.
title_sort f420h2 dependent degradation of aflatoxin and other furanocoumarins is widespread throughout the actinomycetales
url http://europepmc.org/articles/PMC3288000?pdf=render
work_keys_str_mv AT gaurivlapalikar f420h2dependentdegradationofaflatoxinandotherfuranocoumarinsiswidespreadthroughouttheactinomycetales
AT matthewctaylor f420h2dependentdegradationofaflatoxinandotherfuranocoumarinsiswidespreadthroughouttheactinomycetales
AT andrewcwarden f420h2dependentdegradationofaflatoxinandotherfuranocoumarinsiswidespreadthroughouttheactinomycetales
AT colinscott f420h2dependentdegradationofaflatoxinandotherfuranocoumarinsiswidespreadthroughouttheactinomycetales
AT robynjrussell f420h2dependentdegradationofaflatoxinandotherfuranocoumarinsiswidespreadthroughouttheactinomycetales
AT johngoakeshott f420h2dependentdegradationofaflatoxinandotherfuranocoumarinsiswidespreadthroughouttheactinomycetales