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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.<\/jats:p>","DOI":"10.1021\/acs.jafc.6c06419","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T10:01:41Z","timestamp":1789120901000},"page":"28952-28969","source":"Crossref","is-referenced-by-count":0,"title":["Advances in Metabolic\nEngineering for Biosynthesis\nof 5-Aminolevulinic Acid"],"prefix":"10.1021","volume":"74","author":[{"given":"Yuanyuan","family":"Sha","sequence":"first","affiliation":[{"name":"Nanjing University of Science and Technology , , ,","place":["Nanjing, China, 210094"]},{"name":"Nanjing University of Science and Technology , , ,","place":["Nanjing, China, 210094"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zixin","family":"Teng","sequence":"additional","affiliation":[{"name":"Nanjing University of Science and Technology , , ,","place":["Nanjing, China, 210094"]},{"name":"Nanjing University of Science and Technology , , ,","place":["Nanjing, China, 210094"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mianshen","family":"Ge","sequence":"additional","affiliation":[{"name":"Nanjing University of Science and Technology , , ,","place":["Nanjing, China, 210094"]},{"name":"Nanjing University of Science and Technology , , ,","place":["Nanjing, China, 210094"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Liu","sequence":"additional","affiliation":[{"name":"Nanjing University of Science and Technology , , ,","place":["Nanjing, China, 210094"]},{"name":"Nanjing University of Science and Technology , , ,","place":["Nanjing, China, 210094"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juncheng","family":"Huo","sequence":"additional","affiliation":[{"name":"Nanjing University of Science and Technology , , ,","place":["Nanjing, China, 210094"]},{"name":"Nanjing University of Science and Technology , , ,","place":["Nanjing, China, 210094"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxin","family":"Li","sequence":"additional","affiliation":[{"name":"Nanjing University of Science and Technology , , ,","place":["Nanjing, China, 210094"]},{"name":"Nanjing University of Science and Technology , , ,","place":["Nanjing, China, 210094"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinod","family":"Kumar","sequence":"additional","affiliation":[{"name":"University of Houston , , , ,","place":["Sugar Land, Texas, United States, 77479"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0094-3178","authenticated-orcid":true,"given":"Zhaoxian","family":"Xu","sequence":"additional","affiliation":[{"name":"Nanjing University of Science and Technology , , ,","place":["Nanjing, China, 210094"]},{"name":"Nanjing University of Science and Technology , , ,","place":["Nanjing, China, 210094"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Zhai","sequence":"additional","affiliation":[{"name":"Nanjing University of Science and Technology , , ,","place":["Nanjing, China, 210094"]},{"name":"Nanjing University of Science and Technology , , ,","place":["Nanjing, China, 210094"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9493-305X","authenticated-orcid":true,"given":"Mingjie","family":"Jin","sequence":"additional","affiliation":[{"name":"Nanjing University of Science and Technology , , ,","place":["Nanjing, China, 210094"]},{"name":"Nanjing University of Science and Technology , , ,","place":["Nanjing, China, 210094"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,11]]},"reference":[{"issue":"1","key":"2026092310065599700_cit1","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1080\/07388551.2024.2336532","article-title":"A comprehensive review on the recent\nadvances for 5-aminolevulinic acid production by the engineered bacteria","volume":"45","author":"Chen","year":"2025","journal-title":"Crit. 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