Recent Advances in Engineering Microbial Cell Factories for Tryptophan-Derived Chemicals.

Tryptophan-derived metabolites are indole-containing compounds with applications in medicine, functional foods, and agriculture. Conventional production via plant extraction or chemical synthesis is often inefficient and unsustainable, prompting the development of microbial biosynthesis. In this review, these metabolites are classified based on reaction sites and the extent of l-tryptophan scaffold remodeling into side-chain-modified compounds, indole ring-functionalized compounds, oxidative coupling products, and complex indole alkaloids, providing a framework to compare biosynthetic logic across pathways. Within this context, recent advances in metabolic engineering focus on improving catalytic performance, pathway balance, and cellular robustness through enzyme engineering combined with high-throughput screening, advanced genetic tools and dynamic regulatory systems, and cellular engineering strategies such as coculture design and membrane or transporter engineering. These developments provide a basis for further integration of artificial intelligence, computational design, and bioprocess optimization to enhance the efficiency and scalability of microbial production.