Design of Stable and Self-regulated Microbial Consortia for Chemical Synthesis

Overview

Journal Nat Commun

Specialty Biology

Date 2022 Mar 24

PMID 35322005

Authors

Xianglai Li

Zhao Zhou

Wenna Li

Yajun Yan

Xiaolin Shen

Jia Wang

Xinxiao Sun

Qipeng Yuan

Affiliations

Soon will be listed here.

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.

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