title: Identified biosynthetic pathway of aspergiolide A and a novel strategy to increase its production in a marine-derived fungus Aspergillus glaucus by feeding of biosynthetic precursors and inhibitors simultaneously.
abstract: Aspergiolide A is a novel anti-tumor anthraquinone derivant produced by marine-derived fungus Aspergillus glaucus. To identify its biosynthetic pathway and further improve the production, the effects of biosynthetic pathway specific inhibitors and precursors were investigated. Cerulenin and iodoacetamide, the specific inhibitors of polyketide pathway, could completely inhibit the aspergiolide A accumulation. Putative precursors of polyketide pathway could increase aspergiolide A production greatly, such as 6 mM acetate increased production by 135%. Simvastatin and citrate, the inhibitors of mevalonate pathway, stimulated the production by 63% and 179%, respectively. Considering that acetyl-CoA is the common starter unit in both polyketide and mevalonate pathway, a novel strategy was designed to stimulate the aspergiolide A accumulation. Combinations of 12 mM acetate with 0.3 mM simvastatin could increase the production by 151%, while the supplementation with 12 mM acetate and 12 mM citrate brought a 262% increase of aspergiolide A production. The strategy might be very useful to enhance the production of other secondary metabolites derived from polyketide pathway.
authors.affiliation: State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, China.
authors.forename: Xueqian
authors.initials: X
authors.lastname: Sun
authors.forename: Xiangshan
authors.initials: X
authors.lastname: Zhou
authors.forename: Menghao
authors.initials: M
authors.lastname: Cai
authors.forename: Kejing
authors.initials: K
authors.lastname: Tao
authors.forename: Yuanxing
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000085:Acetates / Q000494:pharmacology; D000880:Anthraquinones / Q000037:antagonists & inhibitors / Q000138:chemical synthesis*; D001230:Aspergillus / Q000378:metabolism*; D008386:Marine Biology; D008798:Mevalonic Acid / Q000037:antagonists & inhibitors; D012765:Shikimic Acid / Q000037:antagonists & inhibitors; D019821:Simvastatin / Q000494:pharmacology
chemical_list: D000085:Acetates; D000880:Anthraquinones; C542894:aspergiolide A; D012765:Shikimic Acid; D019821:Simvastatin; D008798:Mevalonic Acid