title: New insight into the ochratoxin A biosynthetic pathway through deletion of a nonribosomal peptide synthetase gene in Aspergillus carbonarius.
abstract: Ochratoxin A (OTA), a mycotoxin produced by Aspergillus and Penicillium species, is composed of a dihydroisocoumarin ring linked to phenylalanine, and its biosynthetic pathway has not yet been completely elucidated. Most of the knowledge regarding the genetic and enzymatic aspects of OTA biosynthesis has been elucidated in Penicillium species. In Aspergillus species, only pks genes involved in the initial steps of the pathway have been partially characterized. In our study, the inactivation of a gene encoding a nonribosomal peptide synthetase (NRPS) in OTA-producing A. carbonarius ITEM 5010 has eliminated the ability of this fungus to produce OTA. This is the first report on the involvement of an nrps gene product in OTA biosynthetic pathway in an Aspergillus species. The absence of OTA and ochratoxin α, the isocoumaric derivative of OTA, and the concomitant increase of ochratoxin β, the dechloro analog of ochratoxin α, were observed in the liquid culture of transformed strain. The data provide the first evidence that the enzymatic step adding phenylalanine to polyketide dihydroisocoumarin precedes the chlorination step to form OTA in A. carbonarius and that ochratoxin α is a product of hydrolysis of OTA, giving an interesting new insight into the biosynthetic pathway of the toxin.
authors.affiliation: Institute of Sciences of Food Production (ISPA), National Research Council (CNR), Bari, Italy. antonia.gallo@ispa.cnr.it
authors.forename: Antonia
authors.initials: A
authors.lastname: Gallo
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Bruno
authors.forename: Michele
authors.initials: M
authors.lastname: Solfrizzo
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Perrone
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Mulè
authors.forename: Angelo
authors.initials: A
authors.lastname: Visconti
authors.forename: Scott E
authors.initials: SE
authors.lastname: Baker
mesh_terms: D001230:Aspergillus / Q000201:enzymology* / Q000235:genetics*; D053898:Biosynthetic Pathways / Q000235:genetics*; D003470:Culture Media / Q000737:chemistry; D009793:Ochratoxins / Q000096:biosynthesis*; D010453:Peptide Synthases / Q000235:genetics* / Q000378:metabolism*; D017384:Sequence Deletion
chemical_list: D003470:Culture Media; D009793:Ochratoxins; C025589:ochratoxin A; D010453:Peptide Synthases; C104385:non-ribosomal peptide synthase