Advances in Metabolic Engineering for Biosynthesis of 5-Aminolevulinic Acid

Q: What does this research mean for the field?

Microbial cell factories, optimized through metabolic engineering and synthetic biology approaches such as enzyme and pathway optimization, serve as promising platforms for the efficient and sustainable production of 5-aminolevulinic acid (5-ALA). Novelty: ClaimNovelty.SYNTHESIS. Consensus alignment: ConsensusAlignment.NEUTRAL.

Yuanyuan Sha; Zixin Teng; Mianshen Ge; Zheng Liu; Juncheng Huo; Jiaxin Li; Vinod Kumar; Zhaoxian Xu; Rui Zhai; Mingjie Jin

doi:10.1021/acs.jafc.6c06419

September 11, 2026Journal of Agricultural and Food Chemistry

Advances in Metabolic Engineering for Biosynthesis of 5-Aminolevulinic Acid

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Key Points

To review the biosynthetic pathways and metabolic engineering interventions developed to optimize microbial production of 5-aminolevulinic acid (5-ALA).
Synthesized recent literature detailing the primary metabolic routes for 5-ALA biosynthesis.
Evaluated advancements across enzyme engineering, pathway optimization, and cellular host engineering applied to microbial cell factories.
Categorized key native and synthetic enzymatic pathways governing precursor flux toward 5-ALA synthesis in engineered microbes.
Identified combined approaches—including catalytic enzyme enhancement, regulatory circuit rewiring, and metabolic flux balancing—as critical drivers of improved 5-ALA titer and productivity.
Outlined persistent industrial challenges, such as by-product accumulation and metabolic burden, while proposing rational cell design strategies for future scale-up.

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Implication

Review outlines metabolic engineering strategies to enhance 5-aminolevulinic acid production in microbial cell factories, highlighting pathways for sustainable industrial biomanufacturing.

Abstract

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.

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Sha et al. (2026) studied this question.

synapsesocial.com/papers/6aa7b32d0926e14a848b1e6b https://doi.org/10.1021/acs.jafc.6c06419

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Advances in Metabolic Engineering for Biosynthesis of 5-Aminolevulinic Acid

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Advances in Metabolic Engineering for Biosynthesis of 5-Aminolevulinic Acid

Key Points

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Implication

Abstract

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