期刊
ACS SYNTHETIC BIOLOGY
卷 9, 期 6, 页码 1240-1245出版社
AMER CHEMICAL SOC
DOI: 10.1021/acssynbio.0c00065
关键词
fermentation; glucose; tryptophan; E. coli; high titer
资金
- Novo Nordisk Foundation [NNF10CC1016517]
Melatonin is a commercially attractive tryptophan-derived hormone. Here we describe a bioprocess for the production of melatonin using Escherichia coli to high titers. The first engineered strain produced 0.13 g/L of melatonin from tryptophan under fed-batch fermentation conditions. A 4-fold improvement on melatonin titer was further achieved by (1) protein engineering of rate-limiting tryptophan hydroxylase to improve 5-hydroxytryptophan biosynthesis and (2) chromosomal integration of aromatic-amino-acid decarboxylase to limit byproduct formation and to minimize gene toxicity to the host cell. Fermentation optimization improved melatonin titer by an additional 2-fold. Deletion of yddG, a tryptophan exporter, exhibited an additive beneficial effect. The final engineered strain produced similar to 2.0 g/L of melatonin with tryptophan supplemented externally and similar to 1.0 g/L with glucose as the sole carbon source for tryptophan supply. This study lays the foundation for further developing a commercial melatonin-producing E. coli strain.
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