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Screening non-conventional yeasts for acid tolerance and engineering Pichia occidentalis for production of muconic acid
Saccharomyces cerevisiae is a workhorse of industrial biotechnology owing to the organism’s prominence in alcohol fermentation and the suite of sophisticated genetic tools available to manipulate its metabolism. However, S. cerevisiae is not suited to overproduce many bulk bioproducts, as toxicity c...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10471774/ https://www.ncbi.nlm.nih.gov/pubmed/37652930 http://dx.doi.org/10.1038/s41467-023-41064-5 |
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author | Pyne, Michael E. Bagley, James A. Narcross, Lauren Kevvai, Kaspar Exley, Kealan Davies, Meghan Wang, Qingzhao Whiteway, Malcolm Martin, Vincent J. J. |
author_facet | Pyne, Michael E. Bagley, James A. Narcross, Lauren Kevvai, Kaspar Exley, Kealan Davies, Meghan Wang, Qingzhao Whiteway, Malcolm Martin, Vincent J. J. |
author_sort | Pyne, Michael E. |
collection | PubMed |
description | Saccharomyces cerevisiae is a workhorse of industrial biotechnology owing to the organism’s prominence in alcohol fermentation and the suite of sophisticated genetic tools available to manipulate its metabolism. However, S. cerevisiae is not suited to overproduce many bulk bioproducts, as toxicity constrains production at high titers. Here, we employ a high-throughput assay to screen 108 publicly accessible yeast strains for tolerance to 20 g L(−1) adipic acid (AA), a nylon precursor. We identify 15 tolerant yeasts and select Pichia occidentalis for production of cis,cis-muconic acid (CCM), the precursor to AA. By developing a genome editing toolkit for P. occidentalis, we demonstrate fed-batch production of CCM with a maximum titer (38.8 g L(−1)), yield (0.134 g g(−1) glucose) and productivity (0.511 g L(−1) h(−1)) that surpasses all metrics achieved using S. cerevisiae. This work brings us closer to the industrial bioproduction of AA and underscores the importance of host selection in bioprocessing. |
format | Online Article Text |
id | pubmed-10471774 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-104717742023-09-02 Screening non-conventional yeasts for acid tolerance and engineering Pichia occidentalis for production of muconic acid Pyne, Michael E. Bagley, James A. Narcross, Lauren Kevvai, Kaspar Exley, Kealan Davies, Meghan Wang, Qingzhao Whiteway, Malcolm Martin, Vincent J. J. Nat Commun Article Saccharomyces cerevisiae is a workhorse of industrial biotechnology owing to the organism’s prominence in alcohol fermentation and the suite of sophisticated genetic tools available to manipulate its metabolism. However, S. cerevisiae is not suited to overproduce many bulk bioproducts, as toxicity constrains production at high titers. Here, we employ a high-throughput assay to screen 108 publicly accessible yeast strains for tolerance to 20 g L(−1) adipic acid (AA), a nylon precursor. We identify 15 tolerant yeasts and select Pichia occidentalis for production of cis,cis-muconic acid (CCM), the precursor to AA. By developing a genome editing toolkit for P. occidentalis, we demonstrate fed-batch production of CCM with a maximum titer (38.8 g L(−1)), yield (0.134 g g(−1) glucose) and productivity (0.511 g L(−1) h(−1)) that surpasses all metrics achieved using S. cerevisiae. This work brings us closer to the industrial bioproduction of AA and underscores the importance of host selection in bioprocessing. Nature Publishing Group UK 2023-08-31 /pmc/articles/PMC10471774/ /pubmed/37652930 http://dx.doi.org/10.1038/s41467-023-41064-5 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Pyne, Michael E. Bagley, James A. Narcross, Lauren Kevvai, Kaspar Exley, Kealan Davies, Meghan Wang, Qingzhao Whiteway, Malcolm Martin, Vincent J. J. Screening non-conventional yeasts for acid tolerance and engineering Pichia occidentalis for production of muconic acid |
title | Screening non-conventional yeasts for acid tolerance and engineering Pichia occidentalis for production of muconic acid |
title_full | Screening non-conventional yeasts for acid tolerance and engineering Pichia occidentalis for production of muconic acid |
title_fullStr | Screening non-conventional yeasts for acid tolerance and engineering Pichia occidentalis for production of muconic acid |
title_full_unstemmed | Screening non-conventional yeasts for acid tolerance and engineering Pichia occidentalis for production of muconic acid |
title_short | Screening non-conventional yeasts for acid tolerance and engineering Pichia occidentalis for production of muconic acid |
title_sort | screening non-conventional yeasts for acid tolerance and engineering pichia occidentalis for production of muconic acid |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10471774/ https://www.ncbi.nlm.nih.gov/pubmed/37652930 http://dx.doi.org/10.1038/s41467-023-41064-5 |
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