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Updated: Oct 11, 2026

A Customizable Approach for the Enzymatic Production and Purification of Diterpenoid Natural Products
Published on: October 4, 2019
Engineering microbial platforms for diversified biosynthesis of antidepressant tryptophan-derived neuroactive
Ruirui Xu1, Fengling Yang2, Luyao Zhang2
1The Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi, China; The Science Center for Future Foods, Jiangnan University, Wuxi 214122, China; The Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi, China; State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi 214122, China.
Abstract:
Tryptophan-drived neuroactive compounds, including serotonin, melatonin, 5-hydroxytryptophan (5-HTP), psilocybin, and related indole derivatives, represent an important class of therapeutics for depression and other neuropsychiatric disorders. However, conventional production through chemical synthesis or natural extraction remains limited by low sustainability, poor selectivity, and high manufacturing costs. Advances in synthetic biology, metabolic engineering, and enzyme engineering have enabled the development of microbial cell factories for the efficient biosynthesis of these high-value compounds. This Review highlights recent progress in engineering microbial platforms for antidepressant tryptophan derivatives, focusing on tryptophan overproduction, hydroxylation biocatalysts, downstream biosynthetic pathways, and cofactor engineering. We further discuss the emerging roles of bacterial heme-dependent tryptophan hydroxylases and AI-assisted enzyme and pathway engineering in expanding the biosynthetic toolbox. Finally, we outline current challenges and future opportunities for integrating intelligent strain design with advanced bioprocess engineering to advance the biomanufacturing of tryptophan-derived neuroactives.
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