Microbial Chassis Development for Natural Product Biosynthesis

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. 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. 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. a computer device mimicking human thought processes, learning capacity, and knowledge storage, which can be used for modeling and database construction. a transcription factor or riboswitch enabling the regulation of cellular processes by responding to a specific signal chemical. Biosensors can be integrated into gene circuits to dynamically regulate gene expression. a platform cell for the production of a variety of chemicals or enzymes by integrating corresponding synthetic biology modules into the cell. a genome editing tool that will cause DNA double strands to break at a target position. a method of accelerating strain evolution to obtain desired characteristics by creating a selection-pressure environment. a novel synthetic biology strategy to dynamically regulate gene expression using biosensor-based genetic circuits, which can be used to decouple cell growth and product synthesis by chassis cells and reduce the accumulation of intermediate metabolites. a regulatory module comprising a signal input part, a controller, and a signal output part. Complex logic gates can be built between different genetic circuits to achieve fine control of gene expression. a method for rapid, automated strain screening and detection by introducing a reporting system into the strain. a basic concept in synthetic biology. It aims to divide the complex metabolic network in microbes into different parts to facilitate overall control, including product synthesis modules, competition modules, cell growth modules, and so on. a mRNA sequence with a specific structure that responds to small molecules and has regulatory functions. The secondary structure of a riboswitch will be changed when combined with specific small molecules, further affecting the transcription and translation of downstream genes. a discipline of de novo construction of new cell factories or the redesign of the enzymes, metabolic networks, and regulatory systems of existing organisms to produce specific chemicals. This discipline focuses on building standardized, modular, and uncoupled components and finally builds or reprograms the artificial biosystem by assembling and integrating these modules.