Improved pestalotiollide B production by deleting competing polyketide synthase genes in Pestalotiopsis microspora

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• 作者：Longfei Chen ; Yingying Li ; Qian Zhang…
• 关键词：CETP inhibitor ; Dibenzodioxocinones ; Fermentation improvement ; Polyketide ; Pestalotiollide B
• 刊名：Journal of Industrial Microbiology & Biotechnology
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：44
• 期：2
• 页码：237-246
• 全文大小：
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Microbiology; Biochemistry, general; Inorganic Chemistry; Genetic Engineering; Biotechnology; Bioinformatics;
• 出版者：Springer Berlin Heidelberg
• ISSN：1476-5535
• 卷排序：44

文摘

Pestalotiollide B, an analog of dibenzodioxocinones which are inhibitors of cholesterol ester transfer proteins, is produced by Pestalotiopsis microspora NK17. To increase the production of pestalotiollide B, we attempted to eliminate competing polyketide products by deleting the genes responsible for their biosynthesis. We successfully deleted 41 out of 48 putative polyketide synthases (PKSs) in the genome of NK17. Nine of the 41 PKS deleted strains had significant increased production of pestalotiollide B (P < 0.05). For instance, deletion of pks35, led to an increase of pestalotiollide B by 887%. We inferred that these nine PKSs possibly lead to branch pathways that compete for precursors with pestalotiollide B, or that convert the product. Deletion of some other PKS genes such as pks8 led to a significant decrease of pestalotiollide B, suggesting they are responsible for its biosynthesis. Our data demonstrated that improvement of pestalotiollide B production can be achieved by eliminating competing polyketides.