Developing a pathway-independent and full-autonomous global resource allocation strategy to dynamically switching phenotypic states

Nat Commun. 2020 Nov 2;11(1):5521. doi: 10.1038/s41467-020-19432-2.

Abstract

A grand challenge of biological chemical production is the competition between synthetic circuits and host genes for limited cellular resources. Quorum sensing (QS)-based dynamic pathway regulations provide a pathway-independent way to rebalance metabolic flux over the course of the fermentation. Most cases, however, these pathway-independent strategies only have capacity for a single QS circuit functional in one cell. Furthermore, current dynamic regulations mainly provide localized control of metabolic flux. Here, with the aid of engineering synthetic orthogonal quorum-related circuits and global mRNA decay, we report a pathway-independent dynamic resource allocation strategy, which allows us to independently controlling two different phenotypic states to globally redistribute cellular resources toward synthetic circuits. The strategy which could pathway-independently and globally self-regulate two desired cell phenotypes including growth and production phenotypes could totally eliminate the need for human supervision of the entire fermentation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biocatalysis
  • Biosynthetic Pathways / genetics
  • Escherichia coli / genetics
  • Escherichia coli / metabolism*
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / metabolism
  • Fatty Acids / metabolism*
  • Fermentation / genetics
  • Gene Expression Regulation, Bacterial
  • Metabolic Engineering / methods*
  • Quorum Sensing / genetics*
  • RNA Stability / genetics*

Substances

  • Escherichia coli Proteins
  • Fatty Acids