title: Polyketides in Aspergillus terreus: biosynthesis pathway discovery and application.
abstract: The knowledge of biosynthesis gene clusters, production improving methods, and bioactivity mechanisms is very important for the development of filamentous fungi metabolites. Metabolic engineering and heterologous expression methods can be applied to improve desired metabolite production, when their biosynthesis pathways have been revealed. And, stable supplement is a necessary basis of bioactivity mechanism discovery and following clinical trial. Aspergillus terreus is an outstanding producer of many bioactive agents, and a large part of them are polyketides. In this review, we took polyketides from A. terreus as examples, focusing on 13 polyketide synthase (PKS) genes in A. terreus NIH 2624 genome. The biosynthesis pathways of nine PKS genes have been reported, and their downstream metabolites are lovastatin, terreic acid, terrein, geodin, terretonin, citreoviridin, and asperfuranone, respectively. Among them, lovastatin is a well-known hypolipidemic agent. Terreic acid, terrein, citreoviridin, and asperfuranone show good bioactivities, especially anticancer activities. On the other hand, geodin and terretonin are mycotoxins. So, biosynthesis gene cluster information is important for the production or elimination of them. We also predicted three possible gene clusters that contain four PKS genes by homologous gene alignment with other Aspergillus strains. We think that this is an effective way to mine secondary metabolic gene clusters.
authors.affiliation: State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237, China. yy1047@126.com.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yin
authors.affiliation: State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237, China.
authors.forename: Menghao
authors.initials: M
authors.lastname: Cai
authors.affiliation: State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237, China.
authors.forename: Xiangshan
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Marine Biotechnology Laboratory, State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, 200240, China.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Li
authors.affiliation: State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237, China. yxzhang@ecust.edu.cn.|Shanghai Collaborative Innovation Center for Biomanufacturing, 130 Meilong Road, Shanghai, 200237, China. yxzhang@ecust.edu.cn.
authors.forename: Yuanxing
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D001230:Aspergillus / Q000235:genetics* / Q000378:metabolism*; D001688:Biological Products / Q000378:metabolism*; D053898:Biosynthetic Pathways; D015870:Gene Expression; D060847:Metabolic Engineering / Q000379:methods; D005810:Multigene Family; D061065:Polyketides / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D001688:Biological Products; D061065:Polyketides; D011994:Recombinant Proteins
keywords: Aspergillus terreus; Biosynthesis pathway; Gene cluster; Heterologous expression; Polyketide