https://video.igem.org/videos/watch/c1515a2a-0538-40ef-9476-f7b38511e60f Title: Symphony in the cell:Biomanufacturing of 5-Hydroxytryptophan via Multi-Scale Engineering Description: The global burden of mental health disorders highlight the need for efficient production of bioactive compounds 5-Hydroxytryptophan (5-HTP) due to its outstanding physiological functions in regulating mood and treating depression. Sustainable biomanufacturing of 5-HTP using microbial synthesis offers attractive application prospects. However, it suffers from inherent bottlenecks including low tryptophan hydroxylase activity, inadequate cofactor regeneration, and difficulties in fermentation scale-up. We combined enzyme mining, AI-assisted protein engineering, expression optimization, and model-assisted fermentation to overcome these bottlenecks. Structure-guided design and protein language models generated a TPH7 quadruple mutant with 5.6-fold higher activity than its parent. Reconstructing tetrahydrobiopterin biosynthesis and regeneration enabled 5-HTP production in a tryptophan-producing Escherichia coli chassis. Following optimization of the fermentation contitions, the final engineered strain produced 20.0 g/L 5-HTP in 5 L bioreactor without exogenous tryptophan. This work offers an multi-level regulatory framework and provides reusable tools for synthetic biology. Wiki | Official Page Thu, 29 Oct 2026 22:26:58 GMT https://validator.w3.org/feed/docs/rss2.html PeerTube - https://video.igem.org https://video.igem.org/client/assets/images/icons/icon-1500x1500.png https://video.igem.org/videos/watch/c1515a2a-0538-40ef-9476-f7b38511e60f All rights reserved, unless otherwise specified in the terms specified at https://video.igem.org/about and potential licenses granted by each content's rightholder.