Small NRPS-like enzymes in Aspergillus sections Flavi and Circumdati selectively form substituted pyrazinone metabolites
Aspergillus fungi produce mycotoxins that are detrimental to human and animal health. Two sections of aspergilli are of particular importance to cereal food crops such as corn and barley. Aspergillus section Flavi species like A. flavus and A. parasiticus produce aflatoxins, while section Circumdati...
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Published in | Frontiers in fungal biology Vol. 3; p. 1029195 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
Frontiers Media S.A
26.10.2022
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Subjects | |
Online Access | Get full text |
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Summary: | Aspergillus
fungi produce mycotoxins that are detrimental to human and animal health. Two sections of aspergilli are of particular importance to cereal food crops such as corn and barley.
Aspergillus
section
Flavi
species like
A. flavus
and
A. parasiticus
produce aflatoxins, while section
Circumdati
species like
A. ochraceus
and
A. sclerotiorum
produce ochratoxin A. Mitigating these toxins in food and feed is a critical and ongoing worldwide effort. We have previously investigated biosynthetic gene clusters in
Aspergillus flavus
that are linked to fungal virulence in corn. We found that one such cluster,
asa
, is responsible for the production of aspergillic acid, an iron-binding, hydroxamic acid-containing pyrazinone metabolite. Furthermore, we found that the
asa
gene cluster is present in many other aflatoxin- and ochratoxin-producing aspergilli. The core gene in the
asa
cluster encodes the small nonribosomal peptide synthetase-like (NRPS-like) protein AsaC. We have swapped the
asaC
ortholog from
A. sclerotiorum
into
A. flavus
, replacing its native copy, and have also cloned both
asaC
orthologs into
Saccharomyces cerevisiae
. We show that AsaC orthologs in section
Flavi
and section
Circumdati
, while only containing adenylation-thiolation-reductase (ATR) domains, can selectively biosynthesize distinct pyrazinone natural products: deoxyaspergillic acid and flavacol, respectively. Because pyrazinone natural products and the gene clusters responsible for their production are implicated in a variety of important microbe-host interactions, uncovering the function and selectivity of the enzymes involved could lead to strategies that ultimately benefit human health. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Edited by: Selma Pascale Snini, UMR5503 Laboratoire de Génie Chimique (LGC), France This article was submitted to Fungal Secondary Metabolites and Mycotoxins, a section of the journal Frontiers in Fungal Biology Reviewed by: Wenbing Yin, Institute of Microbiology (CAS), China; Mehdi Razzaghi-Abyaneh, Pasteur Institute of Iran (PII), Iran |
ISSN: | 2673-6128 2673-6128 |
DOI: | 10.3389/ffunb.2022.1029195 |