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Updated: Sep 17, 2025

A High-Yield Streptomyces Transcription-Translation Toolkit for Synthetic Biology and Natural Product Applications
Published on: September 10, 2021
Development of an endogenous quorum-sensing based bifunctional dynamic regulation system for efficient product
Mengyao Yang1, Yifan Zhao1, Ruihui Huang1
1State Key Laboratory of Animal Biotech Breeding and College of Biological Sciences, China Agricultural University, Beijing 100193, China.
Abstract:
Streptomyces species are known for producing a great variety of commercially valuable secondary metabolites, especially antibiotics. However, engineering ofStreptomycesis inflexible due to the lack of dynamic regulation tools. The effective endogenous quorum-sensing (QS) circuits capable of simultaneously and dynamically up- and down-regulating different sets of genes for efficient product synthesis have not yet been developed. Here, by leveraging the endogenous avenolide-mediated QS system, we designed a bifunctional dynamic regulation system in avermectin (AVE)-producing Streptomyces avermitilis, enabling simultaneous dynamic up- and down-regulation of multiple target genes. Using the dynamic up-regulation circuit, we up-regulated key genes involved in precursor supply for AVE production, resulting in a 727.4 % increase in AVE B1a (the most effective AVE component) titer in wild-type (WT) strain. Using the dynamic down-regulation circuit to down-regulate key node genes in TCA cycle, aspartate degradation, and acetate synthesis pathways for redirecting metabolic flux toward AVE production resulted in a 589.6 % increase in B1a titer in WT strain. Combined application of the dynamic up- and down-regulation circuits in WT and high-yield industrial strain A229 resulted in B1a titers 413.9 μg/mL (858.1 % higher than WT value) and 8067.6 μg/mL (25.7 % higher than A229 value). These findings present a novel bifunctional dynamic regulation strategy for strain improvement, with the potential to be easily adapted to other microorganisms with identified endogenous QS systems.
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