Engineering of Saccharomyces cerevisiae for the production of (+)‐ambrein
Abstract The triterpenoid (+)‐ambrein is the major component of ambergris, a coprolite of the sperm whale that can only be rarely found on shores. Upon oxidative degradation of (+)‐ambrein, several fragrance molecules are formed, amongst them (−)‐ambrox, one of the highest valued compounds in the pe...
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crwiley:10.1002/yea.3444 2024-09-15T18:37:35+00:00 Engineering of Saccharomyces cerevisiae for the production of (+)‐ambrein Moser, Sandra Leitner, Erich Plocek, Thomas J. Vanhessche, Koenraad Pichler, Harald 2019 http://dx.doi.org/10.1002/yea.3444 https://onlinelibrary.wiley.com/doi/pdf/10.1002/yea.3444 https://onlinelibrary.wiley.com/doi/full-xml/10.1002/yea.3444 en eng Wiley http://creativecommons.org/licenses/by/4.0/ Yeast volume 37, issue 1, page 163-172 ISSN 0749-503X 1097-0061 journal-article 2019 crwiley https://doi.org/10.1002/yea.3444 2024-08-01T04:24:08Z Abstract The triterpenoid (+)‐ambrein is the major component of ambergris, a coprolite of the sperm whale that can only be rarely found on shores. Upon oxidative degradation of (+)‐ambrein, several fragrance molecules are formed, amongst them (−)‐ambrox, one of the highest valued compounds in the perfume industry. In order to generate a Saccharomyces cerevisiae whole‐cell biocatalyst for the production of (+)‐ambrein, intracellular supply of the squalene was enhanced by overexpression of two central enzymes in the mevalonate and sterol biosynthesis pathway, namely the N‐terminally truncated 3‐hydroxy‐3‐methylglutaryl‐CoA reductase 1 (t HMG ) and the squalene synthase ( ERG9 ). In addition, another key enzyme in sterol biosynthesis, squalene epoxidase ( ERG1 ) was inhibited by an experimentally defined amount of the inhibitor terbinafine in order to reduce flux of squalene towards ergosterol biosynthesis while retaining sufficient activity to maintain cell viability and growth. Heterologous expression of a promiscuous variant of Bacillus megaterium tetraprenyl‐β‐curcumene cyclase ( Bme TC‐D373C), which has been shown to be able to catalyse the conversion of squalene to 3‐deoxyachillol and then further to (+)‐ambrein resulted in production of these triterpenoids in S. cerevisiae for the first time. Triterpenoid yields are comparable with the best microbial production chassis described in literature so far, the methylotrophic yeast Pichia pastoris . Consequently, we discuss similarities and differences of these two yeast species when applied for whole‐cell (+)‐ambrein production. Article in Journal/Newspaper Sperm whale Wiley Online Library Yeast 37 1 163 172 |
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Wiley Online Library |
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English |
description |
Abstract The triterpenoid (+)‐ambrein is the major component of ambergris, a coprolite of the sperm whale that can only be rarely found on shores. Upon oxidative degradation of (+)‐ambrein, several fragrance molecules are formed, amongst them (−)‐ambrox, one of the highest valued compounds in the perfume industry. In order to generate a Saccharomyces cerevisiae whole‐cell biocatalyst for the production of (+)‐ambrein, intracellular supply of the squalene was enhanced by overexpression of two central enzymes in the mevalonate and sterol biosynthesis pathway, namely the N‐terminally truncated 3‐hydroxy‐3‐methylglutaryl‐CoA reductase 1 (t HMG ) and the squalene synthase ( ERG9 ). In addition, another key enzyme in sterol biosynthesis, squalene epoxidase ( ERG1 ) was inhibited by an experimentally defined amount of the inhibitor terbinafine in order to reduce flux of squalene towards ergosterol biosynthesis while retaining sufficient activity to maintain cell viability and growth. Heterologous expression of a promiscuous variant of Bacillus megaterium tetraprenyl‐β‐curcumene cyclase ( Bme TC‐D373C), which has been shown to be able to catalyse the conversion of squalene to 3‐deoxyachillol and then further to (+)‐ambrein resulted in production of these triterpenoids in S. cerevisiae for the first time. Triterpenoid yields are comparable with the best microbial production chassis described in literature so far, the methylotrophic yeast Pichia pastoris . Consequently, we discuss similarities and differences of these two yeast species when applied for whole‐cell (+)‐ambrein production. |
format |
Article in Journal/Newspaper |
author |
Moser, Sandra Leitner, Erich Plocek, Thomas J. Vanhessche, Koenraad Pichler, Harald |
spellingShingle |
Moser, Sandra Leitner, Erich Plocek, Thomas J. Vanhessche, Koenraad Pichler, Harald Engineering of Saccharomyces cerevisiae for the production of (+)‐ambrein |
author_facet |
Moser, Sandra Leitner, Erich Plocek, Thomas J. Vanhessche, Koenraad Pichler, Harald |
author_sort |
Moser, Sandra |
title |
Engineering of Saccharomyces cerevisiae for the production of (+)‐ambrein |
title_short |
Engineering of Saccharomyces cerevisiae for the production of (+)‐ambrein |
title_full |
Engineering of Saccharomyces cerevisiae for the production of (+)‐ambrein |
title_fullStr |
Engineering of Saccharomyces cerevisiae for the production of (+)‐ambrein |
title_full_unstemmed |
Engineering of Saccharomyces cerevisiae for the production of (+)‐ambrein |
title_sort |
engineering of saccharomyces cerevisiae for the production of (+)‐ambrein |
publisher |
Wiley |
publishDate |
2019 |
url |
http://dx.doi.org/10.1002/yea.3444 https://onlinelibrary.wiley.com/doi/pdf/10.1002/yea.3444 https://onlinelibrary.wiley.com/doi/full-xml/10.1002/yea.3444 |
genre |
Sperm whale |
genre_facet |
Sperm whale |
op_source |
Yeast volume 37, issue 1, page 163-172 ISSN 0749-503X 1097-0061 |
op_rights |
http://creativecommons.org/licenses/by/4.0/ |
op_doi |
https://doi.org/10.1002/yea.3444 |
container_title |
Yeast |
container_volume |
37 |
container_issue |
1 |
container_start_page |
163 |
op_container_end_page |
172 |
_version_ |
1810481947336507392 |