Engineering microorganisms for enhanced tolerance to toxic end-products and intermediates

Microbial manufacturing offers a sustainable and environmentally friendly approach for chemical production. However, the inherent toxicity of certain high-value chemicals to microbial cell factories presents a significant challenge, severely constraining production efficiency. To enhance microbial tolerance, extensive synthetic biology strategies have been developed. The cell envelope serves as the primary natural barrier in microorganisms, and both its intrinsic composition, including membrane lipids, membrane proteins, and cell wall components, and the regulation of these components play crucial roles in modulating cellular responses to environmental stress. Engineering strategies targeting intracellular components, such as transcription factors and repair pathways, have demonstrated effectiveness in enhancing microbial tolerance to toxic end-products and intermediates. Additionally, recent advances have focused on extracellular engineering, including biofilm formation and the modulation of intercellular interactions, which have garnered significant scientific interest. This review aims to provide a systematic overview of these strategies and offers insights to facilitate the industrial translation and commercialization of microbial production of toxic end-products and intermediates.