Microbial Chassis Development for Natural Product Biosynthesis

• Published in: Trends in biotechnology (Regular ed.) Vol. 38; no. 7; pp. 779 - 796
• Main Authors: Xu, Xianhao, Liu, Yanfeng, Du, Guocheng, Ledesma-Amaro, Rodrigo, Liu, Long
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.07.2020; Elsevier Limited; Elsevier
• Subjects: Antibiotics; Artificial intelligence; Big Data; Binding sites; biochemical pathways; Biosynthesis; Carbon; Chassis; chassis cells; Construction; E coli; Enzymes; Flavonoids; Functional foods & nutraceuticals; Gene expression; Genetic engineering; genome mining; Genomes; Identification; Internal Medicine; Metabolic engineering; Metabolism; Metabolites; Microorganisms; Natural products; Proteins; Synthetic biology; systems metabolic engineering; chassis cells; natural products; synthetic biology; systems metabolic engineering
• ISSN: 0167-7799; 1879-3096; 1879-3096
• DOI: 10.1016/j.tibtech.2020.01.002

Engineering microbial cells to efficiently synthesize high-value-added natural products has received increasing attention in recent years. In this review, we describe the pipeline to build chassis cells for natural product production. First, we discuss recently developed genome mining strategies for identifying and designing biosynthetic modules and compare the characteristics of different host microbes. Then, we summarize state-of-the-art systems metabolic engineering tools for reconstructing and fine-tuning biosynthetic pathways and transport mechanisms. Finally, we discuss the future prospects of building next-generation chassis cells for the production of natural products. This review provides theoretical guidance for the rational design and construction of microbial strains to produce natural products. Recent advances in omics, in silico modeling analysis and design, and DNA assembly provide big data and various tools to identify, design, and assemble the synthesis modules of natural products.Besides classical strains, various other microorganisms can be used as chassis cells for natural products due to developments in systems biology and synthetic biology.Metabolic engineering based on genetic circuits and novel genome editing tools can optimize the complex pathway of natural products.Biosensor-based high-throughput screening helps to identify transporters for natural products and facilitate their secretion.