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Engineering the methylotrophic yeast Ogataea polymorpha for lactate production from methanol

Introduction: Lactate has gained increasing attention as a platform chemical, particularly for the production of the bioplastic poly-lactic acid (PLA). While current microbial lactate production processes primarily rely on the use of sugars as carbon sources, it is possible to envision a future wher...

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Autores principales: Wefelmeier, Katrin, Schmitz, Simone, Haut, Anna Maria, Otten, Johannes, Jülich, Tobias, Blank, Lars Mathias
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10347679/
https://www.ncbi.nlm.nih.gov/pubmed/37456718
http://dx.doi.org/10.3389/fbioe.2023.1223726
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author Wefelmeier, Katrin
Schmitz, Simone
Haut, Anna Maria
Otten, Johannes
Jülich, Tobias
Blank, Lars Mathias
author_facet Wefelmeier, Katrin
Schmitz, Simone
Haut, Anna Maria
Otten, Johannes
Jülich, Tobias
Blank, Lars Mathias
author_sort Wefelmeier, Katrin
collection PubMed
description Introduction: Lactate has gained increasing attention as a platform chemical, particularly for the production of the bioplastic poly-lactic acid (PLA). While current microbial lactate production processes primarily rely on the use of sugars as carbon sources, it is possible to envision a future where lactate can be produced from sustainable, non-food substrates. Methanol could be such a potential substrate, as it can be produced by (electro)chemical hydrogenation from CO(2). Methods: In this study, the use of the methylotrophic yeast Ogataea polymorpha as a host organism for lactate production from methanol was explored. To enable lactate production in Ogataea polymorpha, four different lactate dehydrogenases were expressed under the control of the methanol-inducible MOX promoter. The L-lactate dehydrogenase of Lactobacillus helveticus performed well in the yeast, and the lactate production of this engineered strain could additionally be improved by conducting methanol fed-batch experiments in shake flasks. Further, the impact of different nitrogen sources and the resulting pH levels on production was examined more closely. In order to increase methanol assimilation of the lactate-producing strain, an adaptive laboratory evolution experiment was performed. Results and Discussion: The growth rate of the lactate-producing strain on methanol was increased by 55%, while at the same time lactate production was preserved. The highest lactate titer of 3.8 g/L in this study was obtained by cultivating this evolved strain in a methanol fed-batch experiment in shake flasks with urea as nitrogen source. This study provides a proof of principle that Ogataea polymorpha is a suitable host organism for the production of lactate using methanol as carbon source. In addition, it offers guidance for the engineering of methylotrophic organisms that produce platform chemicals from CO(2)-derived substrates. With reduced land use, this technology will promote the development of a sustainable industrial biotechnology in the future.
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spelling pubmed-103476792023-07-15 Engineering the methylotrophic yeast Ogataea polymorpha for lactate production from methanol Wefelmeier, Katrin Schmitz, Simone Haut, Anna Maria Otten, Johannes Jülich, Tobias Blank, Lars Mathias Front Bioeng Biotechnol Bioengineering and Biotechnology Introduction: Lactate has gained increasing attention as a platform chemical, particularly for the production of the bioplastic poly-lactic acid (PLA). While current microbial lactate production processes primarily rely on the use of sugars as carbon sources, it is possible to envision a future where lactate can be produced from sustainable, non-food substrates. Methanol could be such a potential substrate, as it can be produced by (electro)chemical hydrogenation from CO(2). Methods: In this study, the use of the methylotrophic yeast Ogataea polymorpha as a host organism for lactate production from methanol was explored. To enable lactate production in Ogataea polymorpha, four different lactate dehydrogenases were expressed under the control of the methanol-inducible MOX promoter. The L-lactate dehydrogenase of Lactobacillus helveticus performed well in the yeast, and the lactate production of this engineered strain could additionally be improved by conducting methanol fed-batch experiments in shake flasks. Further, the impact of different nitrogen sources and the resulting pH levels on production was examined more closely. In order to increase methanol assimilation of the lactate-producing strain, an adaptive laboratory evolution experiment was performed. Results and Discussion: The growth rate of the lactate-producing strain on methanol was increased by 55%, while at the same time lactate production was preserved. The highest lactate titer of 3.8 g/L in this study was obtained by cultivating this evolved strain in a methanol fed-batch experiment in shake flasks with urea as nitrogen source. This study provides a proof of principle that Ogataea polymorpha is a suitable host organism for the production of lactate using methanol as carbon source. In addition, it offers guidance for the engineering of methylotrophic organisms that produce platform chemicals from CO(2)-derived substrates. With reduced land use, this technology will promote the development of a sustainable industrial biotechnology in the future. Frontiers Media S.A. 2023-06-30 /pmc/articles/PMC10347679/ /pubmed/37456718 http://dx.doi.org/10.3389/fbioe.2023.1223726 Text en Copyright © 2023 Wefelmeier, Schmitz, Haut, Otten, Jülich and Blank. https://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
Wefelmeier, Katrin
Schmitz, Simone
Haut, Anna Maria
Otten, Johannes
Jülich, Tobias
Blank, Lars Mathias
Engineering the methylotrophic yeast Ogataea polymorpha for lactate production from methanol
title Engineering the methylotrophic yeast Ogataea polymorpha for lactate production from methanol
title_full Engineering the methylotrophic yeast Ogataea polymorpha for lactate production from methanol
title_fullStr Engineering the methylotrophic yeast Ogataea polymorpha for lactate production from methanol
title_full_unstemmed Engineering the methylotrophic yeast Ogataea polymorpha for lactate production from methanol
title_short Engineering the methylotrophic yeast Ogataea polymorpha for lactate production from methanol
title_sort engineering the methylotrophic yeast ogataea polymorpha for lactate production from methanol
topic Bioengineering and Biotechnology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10347679/
https://www.ncbi.nlm.nih.gov/pubmed/37456718
http://dx.doi.org/10.3389/fbioe.2023.1223726
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