Microbial Synthesis of Human-Hormone Melatonin at Gram Scales
- PMID: 32501000
- DOI: 10.1021/acssynbio.0c00065
Microbial Synthesis of Human-Hormone Melatonin at Gram Scales
Abstract
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.
Keywords: E. coli; fermentation; glucose; high titer; tryptophan.
Similar articles
-
Metabolic engineering of Escherichia coli for efficient production of L-5-hydroxytryptophan from glucose.Microb Cell Fact. 2022 Sep 24;21(1):198. doi: 10.1186/s12934-022-01920-3. Microb Cell Fact. 2022. PMID: 36153615 Free PMC article.
-
Glucose-based microbial production of the hormone melatonin in yeast Saccharomyces cerevisiae.Biotechnol J. 2016 May;11(5):717-24. doi: 10.1002/biot.201500143. Epub 2016 Jan 25. Biotechnol J. 2016. PMID: 26710256 Free PMC article.
-
Genetic engineering of Escherichia coli to enhance production of L-tryptophan.Appl Microbiol Biotechnol. 2013 Sep;97(17):7587-96. doi: 10.1007/s00253-013-5026-3. Epub 2013 Jun 18. Appl Microbiol Biotechnol. 2013. PMID: 23775271
-
Metabolic engineering for improving L-tryptophan production in Escherichia coli.J Ind Microbiol Biotechnol. 2019 Jan;46(1):55-65. doi: 10.1007/s10295-018-2106-5. Epub 2018 Nov 13. J Ind Microbiol Biotechnol. 2019. PMID: 30426284 Review.
-
Melatonin biosynthesis in chicken retina. Regulation of tryptophan hydroxylase and arylalkylamine N-acetyltransferase.Adv Exp Med Biol. 1999;460:31-41. Adv Exp Med Biol. 1999. PMID: 10810497 Review. No abstract available.
Cited by
-
Meta-analysis Driven Strain Design for Mitigating Oxidative Stresses Important in Biomanufacturing.ACS Synth Biol. 2024 Jul 19;13(7):2045-2059. doi: 10.1021/acssynbio.3c00572. Epub 2024 Jun 27. ACS Synth Biol. 2024. PMID: 38934464 Free PMC article.
-
Introducing melatonin to the horticultural industry: physiological roles, potential applications, and challenges.Hortic Res. 2022 Apr 22;9:uhac094. doi: 10.1093/hr/uhac094. eCollection 2022. Hortic Res. 2022. PMID: 35873728 Free PMC article.
-
Metabolic engineering of Escherichia coli for efficient production of L-5-hydroxytryptophan from glucose.Microb Cell Fact. 2022 Sep 24;21(1):198. doi: 10.1186/s12934-022-01920-3. Microb Cell Fact. 2022. PMID: 36153615 Free PMC article.
-
Melatonin biosynthesis pathways in nature and its production in engineered microorganisms.Synth Syst Biotechnol. 2022 Jan 12;7(1):544-553. doi: 10.1016/j.synbio.2021.12.011. eCollection 2022 Mar. Synth Syst Biotechnol. 2022. PMID: 35087957 Free PMC article. Review.
-
Construction of cell factory capable of efficiently converting L-tryptophan into 5-hydroxytryptamine.Microb Cell Fact. 2022 Mar 24;21(1):47. doi: 10.1186/s12934-022-01745-0. Microb Cell Fact. 2022. PMID: 35331215 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
