Finally, perspectives on potential strategies for improving the biosynthesis of 5-ALA and understanding the related mechanisms to further promote its industrial application are conceived and proposed.ĥ-Aminolevulinic acid (5-ALA), also known as δ-aminolevulinic acid, is an oxygen- and nitrogen-containing hydrocarbon. In addition, the detection methods and applications of 5-ALA are also reviewed. The research progress on 5-ALA biosynthesis via the C4/C5 pathway in microbial cells is emphasized, and the corresponding biotechnological design strategies are highlighted and discussed in detail. In this review, the recent progress in biosynthetic pathways and regulatory mechanisms of 5-ALA synthesis in biological hosts are summarized. Because of its potential applications and disadvantages of chemical synthesis, alternative biotechnological methods have drawn increasing attention. 2Key Laboratory of System Microbial Biotechnology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, Chinaĥ-Aminolevulinic acid (5-ALA) is the key precursor for the biosynthesis of tetrapyrrole compounds, with wide applications in medicine, agriculture and other burgeoning fields.1Frontier Science Center for Synthetic Biology (Ministry of Education), Key Laboratory of Systems Bioengineering (Ministry of Education), SynBio Research Platform, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), School of Chemical Engineering and Technology, Tianjin University, Tianjin, China.Meiru Jiang 1 † Kunqiang Hong 1 † Yufeng Mao 2 Hongwu Ma 2 Tao Chen 1 Zhiwen Wang 1*

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