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Towards next-generation model microorganism chassis for biomanufacturing

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Abstract

Synthetic biology provides powerful tools and novel strategies for designing and modifying microorganisms to function as cell factories for biomanufacturing, which is a promising approach for realizing chemical production in a green and sustainable manner. Recent advances in genetic component design and genome engineering have enabled significant progresses in the field of synthetic biology chassis that have been developed for enzymes or biochemical production based on synthetic biology strategies, with particular reference to model microorganisms, such as Escherichia coli, Bacillus subtilis, Corynebacterium glutamicum, and Saccharomyces cerevisiae. In this review, strategies for engineering four different functional cellular modules which encompass the total process of biomanufacturing are discussed, including expanding the substrate spectrum for substrate uptake modules, refactoring biosynthetic pathways and dynamic regulation for product synthesis modules, balancing energy and redox modules, and cell membrane and cell wall engineering of product storage and secretion modules. Novel strategies of integrating and coordinating different cellular modules aided by synthetic co-culturing of multiple chassis, artificial intelligence–aided data mining for guiding strain development, and the process for designing automatic chassis development via biofoundry are expected to generate next generations of model microorganism chassis for more efficient biomanufacturing.

Key points

• Engineering of functional cellular modules facilitate next generations of chassis construction.

• Global optimization of biosynthesis can be improved by metabolic models.

• Data-driven and automatic strain development can improve microorganism chassis construction.

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Funding

This work is financially supported by the National Key Research and Development Program of China (2018YFA0900300), the National Natural Science Foundation of China (31972854, 31622001, 31671845, 21676119), Key Research and Development Program of Jiangsu Province (BE2019628), and National First-class Discipline Program of Light Industry Technology and Engineering (LITE2018-16).

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Authors and Affiliations

  1. Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, Jiangnan University, Wuxi, 214122, China

    Yanfeng Liu, Anqi Su, Jianghua Li, Guocheng Du & Long Liu

  2. Science Center for Future Foods, Jiangnan University, Wuxi, 214122, China

    Yanfeng Liu, Anqi Su, Jianghua Li, Guocheng Du & Long Liu

  3. Department of Bioengineering, Imperial College London, London, SW7 2AZ, UK

    Rodrigo Ledesma-Amaro

  4. Department of Chemical, Biochemical and Environmental Engineering, University of Maryland Baltimore County, Baltimore, MD, 21250, USA

    Peng Xu

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  3. Jianghua Li
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  4. Rodrigo Ledesma-Amaro
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  5. Peng Xu
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  6. Guocheng Du
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  7. Long Liu
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Contributions

YL and LL conceived the topics and wrote the manuscript. AS, JL RL, PX, GD, and LL revised the manuscript. All authors read and approved the manuscript.

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Correspondence to Long Liu.

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Liu, Y., Su, A., Li, J. et al. Towards next-generation model microorganism chassis for biomanufacturing. Appl Microbiol Biotechnol 104, 9095–9108 (2020). https://doi.org/10.1007/s00253-020-10902-7

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