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Updated: Aug 14, 2026

Constructing Cyclic Peptides Using an On-Tether Sulfonium Center
Published on: September 28, 2022
An iterative type I polyketide synthase PKSN catalyzes synthesis of the decaketide alternapyrone with regio-specific
Isao Fujii1, Naho Yoshida, Shigeki Shimomaki
1Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. ifujii@mol.f.u-tokyo.ac.jp
Abstract:
A biosynthetic gene cluster containing five genes, alt1-5, was cloned from Alternaria solani, a causal fungus of early blight disease to tomato and potato. Homology searching indicated that the alt1, 2, and 3 genes code for cytochrome P450s and the alt4 gene for a FAD-dependent oxygenase/oxidase. The alt5 gene encodes a polyketide synthase (PKS), named PKSN, that was found to be an iterative type I complex reduced-type PKS with a C-methyltransferase domain. To identify the PKSN function, the alt5 gene was introduced into the fungal host Aspergillus oryzae under an alpha-amylase promoter. The transformant produced a polyketide compound, named alternapyrone, whose structure is shown to be 3,5-dimethyl-4-hydroxy-6-(1,3,5,7,11,13-hexamethyl-3,5,11-pentadecatrienyl)-pyran-2-one. Labeling experiments confirmed that alternapyrone is a decaketide with octa-methylation from methionine on every C(2) unit except the third unit.
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