Engineering of the Spinosyn PKS:? Directing Starter Unit Incorporation

التفاصيل البيبلوغرافية
العنوان: Engineering of the Spinosyn PKS:? Directing Starter Unit Incorporation
المؤلفون: S. Sheehan, Lesley, E. Lill, Rachel, Wilkinson, Barrie, M. Sheridan, Rose, A. Vousden, William, L. Kaja, Andrew, D. Crouse, Gary, Gifford, James, R. Graupner, Paul, Karr, Laura, Lewer, Paul, C. Sparks, Thomas, F. Leadlay, Peter, Waldron, Clive, J. Martin, Christine
المصدر: Journal of Natural Products; December 2006, Vol. 69 Issue: 12 p1702-1710, 9p
مستخلص: The spinosyns are a family of potent and highly selective insect control agents that display a favorable environmental profile. As some regions of the spinosyn molecule are recalcitrant to chemical modification, a targeted genetic approach was carried out to generate new analogues. The polyketide synthase (PKS) loading modules from the avermectin PKS of Streptomyces avermitilisand the erythromcyin PKS of Saccharopolyspora erythraeawere each used to replace the spinosyn PKS loading module. Both of the resulting strains containing hybrid PKS pathways produced the anticipated spinosyn analogues. Supplementation of the culture media with a range of exogenous carboxylic acids led to the successful incorporation of these novel elements to yield further novel spinosyn molecules, some of which demonstrated potent and new insecticidal activities. Furthermore, it has been demonstrated that semisynthesis of such novel metabolites can then be used to generate active analogues, demonstrating the effectiveness of utilizing these complementary methods to search the chemical space around this template.
قاعدة البيانات: Supplemental Index
الوصف
تدمد:01633864
15206025
DOI:10.1021/np0602517