Advances in Metabolic Engineering for Biosynthesis of 5-Aminolevulinic Acid

Abstract 5-aminolevulinic acid (5-ALA) is a naturally occurring, metabolically active non-proteinogenic amino acid that serves as a key precursor for the biosynthesis of heme, chlorophyll, and vitamin B12. Due to its high biological activity and versatile physiological functions, 5-ALA has been widely applied in agriculture, medicine, and other sectors. With the rapid advances in metabolic engineering and synthetic biology, microbial cell factories have been developed as promising platforms for the efficient production of 5-ALA. This review summarizes recent progress in biosynthetic pathways and metabolic engineering strategies for enhancing 5-ALA production. First, the metabolic routes involved in 5-ALA biosynthesis are outlined. Subsequently, recent advances in engineering approaches, including enzyme engineering, pathway optimization, and cellular engineering, are highlighted. Finally, current challenges and future prospects for sustainable 5-ALA production are discussed. Overall, this review provides valuable insights to guide the rational design and optimization of microbial platforms for enhanced 5-ALA biosynthesis.