title: Rational synthetic pathway refactoring of natural products biosynthesis in actinobacteria.
abstract: Natural products (NPs) and their derivatives are widely used as frontline treatments for many diseases. Actinobacteria spp. are used to produce most of NP antibiotics and have also been intensively investigated for NP production, derivatization, and discovery. However, due to the complicated transcriptional and metabolic regulation of NP biosynthesis in Actinobacteria, especially in the cases of genome mining and heterologous expression, it is often difficult to rationally and systematically engineer synthetic pathways to maximize biosynthetic efficiency. With the emergence of new tools and methods in metabolic engineering, the synthetic pathways of many chemicals, such as fatty acids and biofuels, in model organisms (e.g. Escherichia coli ), have been refactored to realize precise and flexible control of production. These studies also offer a promising approach for synthetic pathway refactoring in Actinobacteria. In this review, the great potential of Actinobacteria as a microbial cell factory for biosynthesis of NPs is discussed. To this end, recent progress in metabolic engineering of NP synthetic pathways in Actinobacteria are summarized and strategies and perspectives to rationally and systematically refactor synthetic pathways in Actinobacteria are highlighted.
authors.affiliation: Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (Wuhan University), Ministry of Education, and Wuhan University School of Pharmaceutical Sciences, Wuhan 430071, China; State Key Laboratory of Bioreactor Engineering, School of Bioengineering, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, China.
authors.forename: Gao-Yi
authors.initials: GY
authors.lastname: Tan
authors.affiliation: Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (Wuhan University), Ministry of Education, and Wuhan University School of Pharmaceutical Sciences, Wuhan 430071, China; Hubei Engineering Laboratory for Synthetic Microbiology, Wuhan Institute of Biotechnology, Wuhan 430075, China. Electronic address: liutg@whu.edu.cn.
authors.forename: Tiangang
authors.initials: T
authors.lastname: Liu
mesh_terms: D039903:Actinobacteria / Q000502:physiology*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001688:Biological Products / Q000302:isolation & purification / Q000378:metabolism*; D053898:Biosynthetic Pathways / Q000502:physiology*; D024861:Genetic Enhancement / Q000379:methods*; D060847:Metabolic Engineering / Q000379:methods*; D064688:Metabolic Flux Analysis / Q000379:methods; D053858:Metabolic Networks and Pathways / Q000502:physiology*; D008954:Models, Biological
chemical_list: D001426:Bacterial Proteins; D001688:Biological Products
keywords: Actinobacteria; Metabolic engineering; Natural product; Refactoring; Synthetic pathway