Chen Longfei, Li Yingying, Zhang Qian, Wang Dan, Akhberdi Oren, Wei Dongsheng, Pan Jiao, Zhu Xudong
State Key Program of Microbiology and Department of Microbiology, College of Life Sciences, Nankai University, Tianjin, China.
Beijing Key Laboratory of Genetic Engineering Drug and Biotechnology, Institute of Biochemistry and Biotechnology, College of Life Sciences, Beijing Normal University, Beijing, China.
J Ind Microbiol Biotechnol. 2017 Feb;44(2):237-246. doi: 10.1007/s10295-016-1882-z. Epub 2016 Dec 22.
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.
稻瘟菌素B是二苯并二恶英酮的类似物，而二苯并二恶英酮是胆固醇酯转移蛋白的抑制剂，由微小拟盘多毛孢NK17产生。为了提高稻瘟菌素B的产量，我们试图通过删除负责其生物合成的基因来消除竞争性聚酮化合物产物。我们成功地删除了NK17基因组中48个假定的聚酮合酶（PKS）中的41个。41个PKS缺失菌株中有9个的稻瘟菌素B产量显著增加（P < 0.05）。例如，删除pks35导致稻瘟菌素B增加了887%。我们推断这9个PKS可能导致了与稻瘟菌素B竞争前体的分支途径，或者导致了产物的转化。删除其他一些PKS基因，如pks8，导致稻瘟菌素B显著减少，表明它们负责其生物合成。我们的数据表明，通过消除竞争性聚酮化合物可以提高稻瘟菌素B的产量。
