Microbial Synthesis of Human-Hormone Melatonin at Gram Scales

Hao Luo*, Konstantin Schneider, Ulla Christensen, Yang Lei, Markus Herrgard, Bernhard Palsson, Bernhard Palsson, Bernhard Palsson

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)


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 ∼2.0 g/L of melatonin with tryptophan supplemented externally and ∼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.

Original languageEnglish
Pages (from-to)1240-1245
Number of pages6
JournalACS Synthetic Biology
Issue number6
Publication statusPublished - 19 Jun 2020

Bibliographical note

Funding Information:
Authors acknowledge financial support from the Novo Nordisk Foundation (NNF10CC1016517). Authors thank Christina Lenhard, Camilla C. Andersen, Svetlana Sherstyk, Charlotte Brøchner, Inger R. Madsen, Mette Kristensen, Milica Randelovic, Christoffer Knudsen, and Hanne B. Christensen and Jochen Förster.

Publisher Copyright:
Copyright © 2020 American Chemical Society.

Other keywords

  • E. coli
  • fermentation
  • glucose
  • high titer
  • tryptophan


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