Microbial factories for lipid: Engineering synthetic routes and regulatory networks for Triacylglycerol biosynthesis

Abstract

Triacylglycerol (TAG) is a crucial energy storage molecule in many living organisms and is indispensable in the bioenergy and food industries. With growing demand for sustainable lipid sources, microbial systems have emerged as a promising alternative to conventional plant- and animal-derived oils. These systems can overcome the environmental and ethical challenges associated with traditional TAG production by leveraging the metabolic versatility of microorganisms. The integration of synthetic biology into microbial lipid biomanufacturing not only aligns with circular bioeconomy principles but also holds great potential to meet global lipid needs sustainably. This review comprehensively summarizes recent advances in microbial TAG production and outlines future research directions, with a focus on: (1) evaluating the TAG accumulation capabilities and synthesis pathways of various oleaginous microorganisms and systematically assessing their potential as chassis cells; and (2) discussing innovative strategies to enhance microbial TAG yields, including the exploration of non-model organisms with high TAG production, increasing precursor supply, optimizing key enzymes in the TAG assembly pathway, integrating bioprocess strategies like co-cultivation, and downstream processing. By bridging foundational lipid biochemistry with advanced metabolic engineering techniques, this work not only advances the theoretical understanding of microbial lipid metabolism but also delivers a systematic technical roadmap for industrial-scale TAG biomanufacturing.

Keywords: Biosynthesis; Oleaginous microorganisms; Synthetic pathway; Triacylglycerol; Triglyceride synthase.