Metabolic engineering of microorganisms for the production of fatty acid-derived biofuels

The intensifying climate crisis necessitates a global transition from fossil fuels to renewable energy sources. To meet this demand, metabolic engineering has become a pivotal strategy for developing microorganisms as efficient cell factories capable of producing fuels and fuel precursors. Among the biofuel platforms, fatty acid-based fuels are particularly promising, offering energy densities comparable to those of petroleum-based fuels. Recent advances in systems metabolic engineering, including metabolic pathway optimization, cofactor balancing, and dynamic regulation, have significantly improved the microbial production of key fuels and intermediates such as alka(e)nes, and fatty acid esters. In this review, we discuss recent progress in metabolic engineering strategies for microbial production of representative fatty acid-based fuels, highlighting current technological challenges and future directions.