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Engineering the Yeast Saccharomyces cerevisiae for the Production of L-(+)-Ergothioneine
L-(+)-Ergothioneine (ERG) is an unusual, naturally occurring antioxidant nutraceutical that has been shown to help reduce cellular oxidative damage. Humans do not biosynthesise ERG, but acquire it from their diet; it exploits a specific transporter (SLC22A4) for its uptake. ERG is considered to be a...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6797849/ https://www.ncbi.nlm.nih.gov/pubmed/31681742 http://dx.doi.org/10.3389/fbioe.2019.00262 |
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author | van der Hoek, Steven A. Darbani, Behrooz Zugaj, Karolina E. Prabhala, Bala Krishna Biron, Mathias Bernfried Randelovic, Milica Medina, Jacqueline B. Kell, Douglas B. Borodina, Irina |
author_facet | van der Hoek, Steven A. Darbani, Behrooz Zugaj, Karolina E. Prabhala, Bala Krishna Biron, Mathias Bernfried Randelovic, Milica Medina, Jacqueline B. Kell, Douglas B. Borodina, Irina |
author_sort | van der Hoek, Steven A. |
collection | PubMed |
description | L-(+)-Ergothioneine (ERG) is an unusual, naturally occurring antioxidant nutraceutical that has been shown to help reduce cellular oxidative damage. Humans do not biosynthesise ERG, but acquire it from their diet; it exploits a specific transporter (SLC22A4) for its uptake. ERG is considered to be a nutraceutical and possible vitamin that is involved in the maintenance of health, and seems to be at too low a concentration in several diseases in vivo. Ergothioneine is thus a potentially useful dietary supplement. Present methods of commercial production rely on extraction from natural sources or on chemical synthesis. Here we describe the engineering of the baker's yeast Saccharomyces cerevisiae to produce ergothioneine by fermentation in defined media. After integrating combinations of ERG biosynthetic pathways from different organisms, we screened yeast strains for their production of ERG. The highest-producing strain was also engineered with known ergothioneine transporters. The effect of amino acid supplementation of the medium was investigated and the nitrogen metabolism of S. cerevisiae was altered by knock-out of TOR1 or YIH1. We also optimized the media composition using fractional factorial methods. Our optimal strategy led to a titer of 598 ± 18 mg/L ergothioneine in fed-batch culture in 1 L bioreactors. Because S. cerevisiae is a GRAS (“generally recognized as safe”) organism that is widely used for nutraceutical production, this work provides a promising process for the biosynthetic production of ERG. |
format | Online Article Text |
id | pubmed-6797849 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-67978492019-11-01 Engineering the Yeast Saccharomyces cerevisiae for the Production of L-(+)-Ergothioneine van der Hoek, Steven A. Darbani, Behrooz Zugaj, Karolina E. Prabhala, Bala Krishna Biron, Mathias Bernfried Randelovic, Milica Medina, Jacqueline B. Kell, Douglas B. Borodina, Irina Front Bioeng Biotechnol Bioengineering and Biotechnology L-(+)-Ergothioneine (ERG) is an unusual, naturally occurring antioxidant nutraceutical that has been shown to help reduce cellular oxidative damage. Humans do not biosynthesise ERG, but acquire it from their diet; it exploits a specific transporter (SLC22A4) for its uptake. ERG is considered to be a nutraceutical and possible vitamin that is involved in the maintenance of health, and seems to be at too low a concentration in several diseases in vivo. Ergothioneine is thus a potentially useful dietary supplement. Present methods of commercial production rely on extraction from natural sources or on chemical synthesis. Here we describe the engineering of the baker's yeast Saccharomyces cerevisiae to produce ergothioneine by fermentation in defined media. After integrating combinations of ERG biosynthetic pathways from different organisms, we screened yeast strains for their production of ERG. The highest-producing strain was also engineered with known ergothioneine transporters. The effect of amino acid supplementation of the medium was investigated and the nitrogen metabolism of S. cerevisiae was altered by knock-out of TOR1 or YIH1. We also optimized the media composition using fractional factorial methods. Our optimal strategy led to a titer of 598 ± 18 mg/L ergothioneine in fed-batch culture in 1 L bioreactors. Because S. cerevisiae is a GRAS (“generally recognized as safe”) organism that is widely used for nutraceutical production, this work provides a promising process for the biosynthetic production of ERG. Frontiers Media S.A. 2019-10-11 /pmc/articles/PMC6797849/ /pubmed/31681742 http://dx.doi.org/10.3389/fbioe.2019.00262 Text en Copyright © 2019 van der Hoek, Darbani, Zugaj, Prabhala, Biron, Randelovic, Medina, Kell and Borodina. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Bioengineering and Biotechnology van der Hoek, Steven A. Darbani, Behrooz Zugaj, Karolina E. Prabhala, Bala Krishna Biron, Mathias Bernfried Randelovic, Milica Medina, Jacqueline B. Kell, Douglas B. Borodina, Irina Engineering the Yeast Saccharomyces cerevisiae for the Production of L-(+)-Ergothioneine |
title | Engineering the Yeast Saccharomyces cerevisiae for the Production of L-(+)-Ergothioneine |
title_full | Engineering the Yeast Saccharomyces cerevisiae for the Production of L-(+)-Ergothioneine |
title_fullStr | Engineering the Yeast Saccharomyces cerevisiae for the Production of L-(+)-Ergothioneine |
title_full_unstemmed | Engineering the Yeast Saccharomyces cerevisiae for the Production of L-(+)-Ergothioneine |
title_short | Engineering the Yeast Saccharomyces cerevisiae for the Production of L-(+)-Ergothioneine |
title_sort | engineering the yeast saccharomyces cerevisiae for the production of l-(+)-ergothioneine |
topic | Bioengineering and Biotechnology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6797849/ https://www.ncbi.nlm.nih.gov/pubmed/31681742 http://dx.doi.org/10.3389/fbioe.2019.00262 |
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