Dynamic control of toxic natural product biosynthesis by an artificial regulatory circuit.

Abstract:

:To mimic the delicately regulated metabolism in nature for improved efficiency, artificial and customized regulatory components for dynamically controlling metabolic networks in multiple layers are essential in laboratory engineering. For this purpose, a novel regulatory component for controlling vanillin biosynthetic pathway was developed through directed evolution, which was responsive to both the product vanillin and substrate ferulic acid, with different capacities. This regulatory component facilitated pathway expression via dynamic control of the intracellular substrate and product concentrations. As vanillin is an antimicrobial compound, low pathway expression and vanillin formation levels enabled better cell growth at an early stage, and the product feedback-activated pathway expression at later stages significantly improved biosynthesis efficiency. This novel multiple-layer dynamic control was demonstrated effective in managing the trade-off between cell growth and production, leading to improved cell growth and vanillin production compared to the conventional or quorum-sensing promoter-controlled pathway. The multiple-layer dynamic control enabled by designed regulatory components responsive to multiple signals shows potential for wide applications in addition to the dynamic controls based on biosynthetic intermediate sensing and quorum sensing reported to date.

journal_name

Metab Eng

journal_title

Metabolic engineering

authors

Liang C,Zhang X,Wu J,Mu S,Wu Z,Jin JM,Tang SY

doi

10.1016/j.ymben.2019.12.002

subject

Has Abstract

pub_date

2020-01-01 00:00:00

pages

239-246

eissn

1096-7176

issn

1096-7184

pii

S1096-7176(19)30323-4

journal_volume

57

pub_type

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