CNR ExploRA

Articolo in rivista, 2021, ENG, 10.3390/toxins13120892

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

Massimo Ferrara 1, Antonia Gallo 2, Carla Cervini 3, Lucia Gambacorta 1, Michele Solfrizzo 1, Scott E. Baker 4,5 and Giancarlo Perrone 1

1 Institute of Sciences of Food Production (ISPA), National Research Council (CNR), 70126 Bari, Italy; lucia.gambacorta@ispa.cnr.it (L.G.); michele.solfrizzo@ispa.cnr.it (M.S.); giancarlo.perrone@ispa.cnr.it (G.P.) 2 Institute of Sciences of Food Production (ISPA), National Research Council (CNR), 73100 Lecce, Italy; antonia.gallo@ispa.cnr.it 3 Applied Mycology Group, Environment and AgriFood Theme, Cranfield University, Cranfield MK43 0AL, UK; carla.cervini@cranfield.ac.uk 4 Functional and Systems Biology Group, Environmental Molecular Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99354, USA; scott.baker@pnnl.gov 5 DOE Joint Bioenergy Institute, Emeryville, CA 94608, USA

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.

Toxins (Basel) 13 (12), pp. 892–?