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Updated: Feb 20, 2026

Hierarchical and Programmable One-Pot Oligosaccharide Synthesis
Published on: September 6, 2019
Programming Low-Molecular-Weight Hyaluronic Acid Biosynthesis in Bacillus amyloliquefaciens Via an Autoinducible
Qian Zhong1,2, Zhen Li1,2, Waibin Duan1,2
1College of Food Science and Light Industry, Nanjing Tech University, Nanjing 211816, P. R. China.
Abstract:
Dynamic metabolic regulation facilitates real-time sensing of pathway states and precise redirection of metabolic flux, thereby enhancing the biosynthesis of diverse value-added compounds. Here, we designed an autoinducible molecular switch in Bacillus amyloliquefaciens by integrating a Pantoea alhagi-derived PaSspB-ssrA* proteolytic system with the DegU-RapG-PhrG quorum-sensing (QS) module. The OFF module employs the novel PaSspB-ssrA* system for targeted degradation of ssrA*-tagged proteins with 86% efficiency, and the ON module utilizes a DegU-activated PispA promoter for cell density-dependent gene expression. To improve hyaluronic acid (HA) production and reduce byproduct accumulation, this system was applied by fusing ssrA* tags into the glycolysis-critical genes pfkA and fruA to attenuate glycolytic flux, together with QS-regulated coexpression of PaSspB and SthHL in engineered Δldh/ΔwbpA/ΔnagB strains, achieving 13.5 ± 0.19 g/L of low-molecular-weight HA (2.89 × 104 Da). The autonomous, inducer-free platform enables cost-effective HA biosynthesis in B. amyloliquefaciens, with broad applicability for synthesizing high-value bioproducts.
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