Evidence of the Involvement of a Cyclase Gene in the Biosynthesis of Ochratoxin A in Aspergillus carbonarius

Ferrara, Massimo; Gallo, Antonia; Cervini, Carla; Gambacorta, Lucia; Solfrizzo, Michele; Baker, Scott E.; Perrone, Giancarlo

doi:10.3390/toxins13120892

Title: Evidence of the Involvement of a Cyclase Gene in the Biosynthesis of Ochratoxin A in Aspergillus carbonarius

Journal Article · Mon Dec 13 00:00:00 EST 2021 · Toxins

DOI:https://doi.org/10.3390/toxins13120892· OSTI ID:1840753

^[1]; Gallo, Antonia ^[2]; Cervini, Carla ^[3]; Gambacorta, Lucia ^[1]; Solfrizzo, Michele ^[1];

^[4];

^[1]

National Research Council (CNR), Bari (Italy). Inst. of Sciences of Food Production (ISPA)
National Research Council (CNR), Lecce (Italy). Inst. of Sciences of Food Production (ISPA)
Cranfield Univ. (United Kingdom)
Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Joint BioEnergy Institute (JBEI), Emeryville, CA (United States)

Ochratoxin A (OTA) is a well-known mycotoxin with wide distribution in food and feed. Fungal genome sequencing has great utility for identifying secondary metabolites gene clusters for known and novel compounds. A comparative analysis of the OTA-biosynthetic cluster in A. steynii, A. westerdijkiae, A. niger, A. carbonarius, and P. nordicum has revealed a high synteny in OTA cluster organization in five structural genes (otaA, otaB, ota, otaR1, and otaD). Moreover, a recent detailed comparative genome analysis of Aspergilli OTA producers led to the identification of a cyclase gene, otaY, located in the OTA cluster between the otaA and otaB genes, encoding for a predicted protein with high similarity to SnoaLs domain. These proteins have been shown to catalyze ring closure steps in the biosynthesis of polyketide antibiotics produced in Streptomyces. In the present study, we demonstrated an upregulation of the cyclase gene in A. carbonarius under OTA permissive conditions, consistent with the expression trends of the other OTA cluster genes and their role in OTA biosynthesis by complete gene deletion. Our results pointed out the involvement of a cyclase gene in OTA biosynthetic pathway for the first time. They represent a step forward in the understanding of the molecular basis of OTA biosynthesis in A. carbonarius.

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Research Organization:: Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER)

Grant/Contract Number:: AC05-76RL01830

OSTI ID:: 1840753

Report Number(s):: PNNL-SA-169400

Journal Information:: Toxins, Vol. 13, Issue 12; ISSN 2072-6651

Publisher:: MDPICopyright Statement

Country of Publication:: United States

Language:: English

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59 BASIC BIOLOGICAL SCIENCES
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polyketide cyclases
CRISPR/Cas9

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