Genetic localization of the orevactaene/epipyrone biosynthetic gene cluster in Epicoccum nigrum

• Published in: Bioorganic & medicinal chemistry letters 2020-07, Vol.30 (14), p.127242-127242, Article 127242
• Main Authors: Lim, Yoon Ji, Choi, Eunha, Park, Si-Hyung, Kwon, Hyung-Jin
• Format: Article
• Language: English
• Subjects: Biosynthetic gene cluster; Epicoccum nigrum; Epipyrone A; Highly-reducing fungal polyketide synthase; Orevactaene
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2020.127242

[Display omitted] •Genome analysis and targeted gene inactivation studies identified the orevactaene/epipyrone (EPN) biosynthetic gene cluster (BGC) in Epicoccum nigrum.•The epnABCD genes in the EPN BGC encode a highly-reducing fungal polyketide synthase, a glycosyltransferase, a cytochrome P450, and a transporter and represent the first blueprint reported to be involved in glycosylated 2-pyrone polyketide biosynthesis.•A wide distribution of EPN BGC homologs in the fungal domain and the bicistronic transcription of epnAB are observed. Epipyrone (EPN)-A (syn. orevactaene) is a polyketide compound of 3-d-galactosyl-4-hydroxy-2-pyrone with a modified heptaene acyl moiety, produced from Epicoccum nigrum and was reported to have various biological activities. Genome analysis identified a hypothetical EPN biosynthetic gene cluster (BGC) composed of the four genes epnABCD, which encode a highly-reducing fungal polyketide synthase, a glycosyltransferase, a cytochrome P450, and a transporter. The individual gene inactivation of epnABC resulted in the total loss of EPN production, while the inactivation of a nearby transcription factor-encoding gene had no effect on the production of EPN, substantiating that epnABCD is the EPN BGC. mRNA expression indicated no epnA transcription in the epnB knockout mutant and the occurrence of the bicistronic transcription of epnAB. This study defined an EPN BGC, which is the first blueprint reported for glycosylated 2-pyrone polyketide biosynthesis.