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Published on: October 4, 2019
Modularity in Enzyme Engineering Enables a High-Yielding Microbial Platform for Melatonin Biosynthesis
Ge Qu1,2, Jincheng Li2, Qing Wang2
1Hubei Hongshan Laboratory, College of Life Science and Technology, Huazhong Agricultural University, Wuhan 430070, China.
None:
The limited availability of structurally specific hydroxylated tryptophan derivatives, whether they are obtained through natural extraction or chemical synthesis, presents challenges for industrial applications. In this study, we report a modular biosynthetic platform in Escherichia coli for producing melatonin and related indoleamines by functionally integrating an animal hydroxylase, an insect decarboxylase, and an avian N-acetyltransferase as well as a plant O-methyltransferase. Following the rational design of key enzymes as well as metabolic pathway optimization, the recombinant strains produced 22.8 g/L of 5-hydroxytryptophan (5-HTP) in a 70 L bioreactor and 6.2 g/L of melatonin in a 5 L bioreactor with exogenous tryptophan feeding. This engineered microbial system establishes an efficient route for manufacturing pharmaceutically relevant tryptophan derivatives and provides a versatile enzymatic toolkit for exploring hydroxylated indole compound biochemistry.
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