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From a Natural Product to Its Biosynthetic Gene Cluster: A Demonstration Using Polyketomycin from Streptomyces diastatochromogenes Tü6028
Published on: January 13, 2017
Novel pyripyropenes produced by gene cluster design and heterologous expression
Shunjin Jia1, Yuchen Wu1, Yihui Chen1
1Ocean College, Zhejiang University, Zhoushan, China.
Abstract:
Post-modification of the isoprenoid ring in pyripyropenes critically modulates their structural diversity and bioactivity. Here, we report the engineered biosynthesis of novel pyripyropene derivatives via reconstruction of the pyripyropene A gene cluster and its heterologous expression in Aspergillus nidulans. Five previously unreported compounds-1-keto-pyripyropene E (1), 13-hydroxy-1-keto-pyripyropene E (2), deacetyl-pyripyropene G (3), 11-deoxo-deacetyl-pyripyropene A (4), and 1-keto-11-deoxo-deacetyl-pyripyropene A (5)-were isolated from the engineered strain. Their structures were unequivocally characterised by MS and NMR spectroscopy, with compounds 1, 2, and 5 representing the first examples of 1-ketone pyripyropenes. Significantly, these 1-ketone derivatives exhibited significantly enhanced insecticidal activity compared to their 1-hydroxy analogues, demonstrating their potential as next-generation insecticide leads.
