Design of stable and self-regulated microbial consortia for chemical synthesis

Xianglai Li, Zhao Zhou, Wenna Li, Yajun Yan, Xiaolin Shen, Jia Wang, Xinxiao Sun () and Qipeng Yuan ()
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Xianglai Li: Beijing University of Chemical Technology
Zhao Zhou: Beijing University of Chemical Technology
Wenna Li: Beijing University of Chemical Technology
Yajun Yan: The University of Georgia
Xiaolin Shen: Beijing University of Chemical Technology
Jia Wang: Beijing University of Chemical Technology
Xinxiao Sun: Beijing University of Chemical Technology
Qipeng Yuan: Beijing University of Chemical Technology

Nature Communications, 2022, vol. 13, issue 1, 1-9

Abstract: Abstract Microbial coculture engineering has emerged as a promising strategy for biomanufacturing. Stability and self-regulation pose a significant challenge for the generation of intrinsically robust cocultures for large-scale applications. Here, we introduce the use of multi-metabolite cross-feeding (MMCF) to establish a close correlation between the strains and the design rules for selecting the appropriate metabolic branches. This leads to an intrinicially stable two-strain coculture where the population composition and the product titer are insensitive to the initial inoculation ratios. With an intermediate-responsive biosensor, the population of the microbial coculture is autonomously balanced to minimize intermediate accumulation. This static-dynamic strategy is extendable to three-strain cocultures, as demonstrated with de novo biosynthesis of silybin/isosilybin. This strategy is generally applicable, paving the way to the industrial application of microbial cocultures.

Date: 2022
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DOI: 10.1038/s41467-022-29215-6

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