Biosynthesis of the mycotoxin tenuazonic acid by a fungal NRPS–PKS hybrid enzyme

• Published in: Nature communications Vol. 6; no. 1; p. 8758
• Main Authors: Yun, Choong-Soo, Motoyama, Takayuki, Osada, Hiroyuki
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 27.10.2015; Nature Publishing Group; Nature Pub. Group
• Subjects: 38; 38/22; 38/61; 38/90; 631/326/421; 631/92/173; 631/92/60; 82/16; 82/83; Fungal Proteins - chemistry; Fungal Proteins - genetics; Fungal Proteins - metabolism; Humanities and Social Sciences; Magnaporthe - classification; Magnaporthe - enzymology; Magnaporthe - genetics; Magnaporthe - metabolism; multidisciplinary; Mycotoxins - biosynthesis; Peptide Synthases - chemistry; Peptide Synthases - genetics; Peptide Synthases - metabolism; Phylogeny; Polyketide Synthases - chemistry; Polyketide Synthases - genetics; Polyketide Synthases - metabolism; Protein Structure, Tertiary; Science; Science (multidisciplinary); Tenuazonic Acid - biosynthesis
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms9758

Tenuazonic acid (TeA) is a well-known mycotoxin produced by various plant pathogenic fungi. However, its biosynthetic gene has been unknown to date. Here we identify the TeA biosynthetic gene from Magnaporthe oryzae by finding two TeA-inducing conditions of a low-producing strain. We demonstrate that TeA is synthesized from isoleucine and acetoacetyl-coenzyme A by TeA synthetase 1 (TAS1). TAS1 is a unique non-ribosomal peptide synthetase and polyketide synthase (NRPS–PKS) hybrid enzyme that begins with an NRPS module. In contrast to other NRPS/PKS hybrid enzymes, the PKS portion of TAS1 has only a ketosynthase (KS) domain and this domain is indispensable for TAS1 activity. Phylogenetic analysis classifies this KS domain as an independent clade close to type I PKS KS domain. We demonstrate that the TAS1 KS domain conducts the final cyclization step for TeA release. These results indicate that TAS1 is a unique type of NRPS–PKS hybrid enzyme. Tenuazonic acid is a mycotoxin produced by various plant pathogenic fungi but its biosynthetic gene is unknown to date. Here, the authors identify the tenuazonic acid biosynthetic gene encoding a protein with a unique KS domain that conducts cyclization step for tenuazonic acid release in Magnaporthe oryzae .