Recent advances in engineering of microbial cell factories for intelligent pH regulation and tolerance

Abstract

pH regulation is a serious concern in the industrial fermentation process as pH adjustment heavily utilizes acid/base and pollutes the environment. Under pH‐stress conditions, microbial growth and production of valuable target products may be severely affected. Furthermore, some strains generating acidic or alkaline products require self pH regulation and increased tolerance against pH‐stress. For pH control, synthetic biology has provided advanced engineering approaches to construct robust and more intelligent microbial strains, exhibiting tolerance to pH‐stress to cope with limitations of pH regulation. This study reviewed the current progress of advanced strain evolution strategies to engineer pH‐stress tolerant strains via synthetic biology. In addition, a large number of pH‐responsive elements, including promoters, riboswitches, and some proteins have been investigated and applied for construction of pH‐responsive genetic circuits and intelligent pH‐responsive microbial strains.

Recent advances in yeast genome evolution with stress tolerance for green biological manufacturing

“…As NHEJ pathway plays a significant role in DSB repair by Ku70 and Ku80, downregulation of NHEJ by disrupting Ku70 and Ku80, and overexpression of HR-associated protein elevate HR rates (J. Gao, Xu, et al, 2021).…”

“…In one study, disruption of Ku80 elevated the HR rate significantly in Ogataea polymorpha ; a thermotolerant yeast exhibiting low homologous recombination (HR) efficiency. As NHEJ pathway plays a significant role in DSB repair by Ku70 and Ku80, downregulation of NHEJ by disrupting Ku70 and Ku80, and overexpression of HR‐associated protein elevate HR rates (J. Gao, Xu, et al, 2021).…”

“…Although the application value of green biological manufacturing has expanded, large‐scale industrial fermentation is affected owing to several limiting factors, including, inadequate contact between microorganisms and raw materials, enhanced partial heat and heat stress, phenotypic limitations of microorganisms, and various pressures during fermentation by different fermentation methods. Furthermore, microbial cell factories also encounter several limitations in terms of high pH (X. Gao, Xu, et al, 2021), high temperature, high product concentration, high osmolarity, high viscosity, and substrate toxicity that lead to slower strain growth, decreased yield, and elevated energy consumption (Deparis et al, 2017). To cope with these limitations, steps should be taken to advance the sustainable development for green biological manufacturing instead of the utilization of fossil fuel at the expense of environmental devastation (Commission on Environment, n.d.).…”

“…Furthermore, microbial cell factories also encounter several limitations in terms of high pH (X. Gao, Xu, et al, 2021), high temperature, high product concentration, high osmolarity, high viscosity, and substrate toxicity that lead to slower strain growth, decreased yield, and elevated energy consumption (Deparis et al, 2017). To cope with these limitations, steps should be taken to advance the sustainable development for green biological manufacturing instead of the utilization of fossil fuel at the expense of environmental devastation (Commission on Environment, n.d.).…”

Synthetic acid stress-tolerance modules improve growth robustness and lysine productivity of industrial Escherichia coli in fermentation at low pH

“…Over the years, several genome-wide evolution engineering strategies have been widely used to enhance the stress resistance for microbial cells [8]. Among them, adaptive laboratory evolution (ALE) is a traditional and commonly used strategy to enhance stress tolerance [9][10][11].…”