title: Improved pestalotiollide B production by deleting competing polyketide synthase genes in Pestalotiopsis microspora.
abstract: 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.
authors.affiliation: State Key Program of Microbiology and Department of Microbiology, College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: Longfei
authors.initials: L
authors.lastname: Chen
authors.affiliation: State Key Program of Microbiology and Department of Microbiology, College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Li
authors.affiliation: State Key Program of Microbiology and Department of Microbiology, College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: State Key Program of Microbiology and Department of Microbiology, College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Wang
authors.affiliation: State Key Program of Microbiology and Department of Microbiology, College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: Oren
authors.initials: O
authors.lastname: Akhberdi
authors.affiliation: State Key Program of Microbiology and Department of Microbiology, College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Wei
authors.affiliation: State Key Program of Microbiology and Department of Microbiology, College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Pan
authors.affiliation: Beijing Key Laboratory of Genetic Engineering Drug and Biotechnology, Institute of Biochemistry and Biotechnology, College of Life Sciences, Beijing Normal University, Beijing, China. zhu11187@bnu.edu.cn.
authors.forename: Xudong
authors.initials: X
authors.lastname: Zhu
mesh_terms: D004926:Escherichia coli / Q000235:genetics; D005656:Fungal Proteins / Q000235:genetics* / Q000378:metabolism; D017353:Gene Deletion; D016681:Genome, Fungal; D007218:Industrial Microbiology; D048630:Polyketide Synthases / Q000235:genetics* / Q000378:metabolism; D061065:Polyketides / Q000378:metabolism*; D013098:Xylariales / Q000235:genetics* / Q000378:metabolism
chemical_list: D005656:Fungal Proteins; D061065:Polyketides; D048630:Polyketide Synthases
keywords: CETP inhibitor; Dibenzodioxocinones; Fermentation improvement; Pestalotiollide B; Polyketide