Engineering of the Spinosyn PKS: Directing Starter Unit Incorporation

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• 作者：Lesley S. Sheehan ; Rachel E. Lill ; Barrie Wilkinson ; Rose M. Sheridan ; William A. Vousden ; Andrew L. Kaja ; Gary D. Crouse ; James Gifford ; Paul R. Graupner ; Laura Karr ; Paul Lewer ; Thomas C. Sparks ; P
• 刊名：Journal of Natural Products
• 出版年：2006
• 出版时间：December 2006
• 年：2006
• 卷：69
• 期：12
• 页码：1702 - 1710
• 全文大小：190K
• 年卷期：v.69,no.12(December 2006)
• ISSN：1520-6025

文摘

The spinosyns are a family of potent and highly selective insect control agents that display a favorable environmentalprofile. As some regions of the spinosyn molecule are recalcitrant to chemical modification, a targeted genetic approachwas carried out to generate new analogues. The polyketide synthase (PKS) loading modules from the avermectin PKSof Streptomyces avermitilis and the erythromcyin PKS of Saccharopolyspora erythraea were each used to replace thespinosyn PKS loading module. Both of the resulting strains containing hybrid PKS pathways produced the anticipatedspinosyn analogues. Supplementation of the culture media with a range of exogenous carboxylic acids led to the successfulincorporation of these novel elements to yield further novel spinosyn molecules, some of which demonstrated potentand new insecticidal activities. Furthermore, it has been demonstrated that semisynthesis of such novel metabolites canthen be used to generate active analogues, demonstrating the effectiveness of utilizing these complementary methods tosearch the chemical space around this template.