Microbial chassis engineering drives heterologous production of complex secondary metabolites
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AbstractThe cryptic secondary metabolite biosynthetic gene clusters (BGCs) far outnumber currently known secondary metabolites. Heterologous production of secondary metabolite BGCs in suitable chassis facilitates yield improvement and discovery of new-to-nature compounds. The two juxtaposed conventional model microorganisms, Escherichia coli, Saccharomyces cerevisiae, have been harnessed as microbial chassis to produce a bounty of secondary metabolites with the help of certain host engineering. In last decade, engineering non-model microbes to efficiently biosynthesize secondary metabolites has received increasing attention due to their peculiar advantages in metabolic networks and/or biosynthesis. The state-of-the-art synthetic biology tools lead the way in operating genetic manipulation in non-model microorganisms for phenotypic optimization or yields improvement of desired secondary metabolites. In this review, we firstly discuss the pros and cons of several model and non-model microbial chassis, as well as the importance of developing broader non-model microorganisms as alternative programmable heterologous hosts to satisfy the desperate needs of biosynthesis study and industrial production. Then we highlight the lately advances in the synthetic biology tools and engineering strategies for optimization of non-model microbial chassis, in particular, the successful applications for efficient heterologous production of multifarious complex secondary metabolites, e.g., polyketides, nonribosomal peptides, as well as ribosomally synthesized and post-translationally modified peptides. Lastly, emphasis is on the perspectives of chassis cells development to access the ideal cell factory in the artificial intelligence-driven genome era. © 2022 Elsevier Inc.
CitationLiu J., Wang X., Dai G., Zhang Y., Bian X. AUTHOR FULL NAMES: Liu, Jiaqi (57201859770); Wang, Xue (57201854159); Dai, Guangzhi (57226801399); Zhang, Youming (55739764500); Bian, Xiaoying (55210908000) 57201859770; 57201854159; 57226801399; 55739764500; 55210908000 Microbial chassis engineering drives heterologous production of complex secondary metabolites (2022) Biotechnology Advances, 59, art. no. 107966, Cited 0 times. DOI: 10.1016/j.biotechadv.2022.107966
Affiliationa Helmholtz International Lab for Anti-Infectives, Shandong University-Helmholtz Institute of Biotechnology, State Key Laboratory of Microbial Technology, Shandong University, Shandong, Qingdao, 266237, China b Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI), Saarland University, Campus E8 1, Saarbrücken, 66123, Germany
Series/Report no.Vol. 59, October 2022
SponsorsNational Natural Science Foundation of China; Natural Science Foundation of Shandong Province; National Key Research and Development Program of China: This work was supported by the National Key R&D Program of China (Grant nos. 2021YFC2100500 , 2019YFA0905700 ), National Natural Science Foundation of China (Grant nos. 32070060 , 32161133013 ), Shandong Provincial Natural Science Foundation (Grant no. ZR2019JQ11 , ZR2019ZD18 ).
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