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Peroxisomal metabolic coupling improves fatty alcohol production from sole methanol in yeast

Methanol is an ideal feedstock for chemical and biological manufacturing. Constructing an efficient cell factory is essential for producing complex compounds through methanol biotransformation, in which coordinating methanol use and product synthesis is often necessary. In methylotrophic yeast, meth...

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Autores principales: Zhai, Xiaoxin, Gao, Jiaoqi, Li, Yunxia, Grininger, Martin, Zhou, Yongjin J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10041095/
https://www.ncbi.nlm.nih.gov/pubmed/36913588
http://dx.doi.org/10.1073/pnas.2220816120
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author Zhai, Xiaoxin
Gao, Jiaoqi
Li, Yunxia
Grininger, Martin
Zhou, Yongjin J.
author_facet Zhai, Xiaoxin
Gao, Jiaoqi
Li, Yunxia
Grininger, Martin
Zhou, Yongjin J.
author_sort Zhai, Xiaoxin
collection PubMed
description Methanol is an ideal feedstock for chemical and biological manufacturing. Constructing an efficient cell factory is essential for producing complex compounds through methanol biotransformation, in which coordinating methanol use and product synthesis is often necessary. In methylotrophic yeast, methanol utilization mainly occurs in peroxisomes, which creates challenges in driving the metabolic flux toward product biosynthesis. Here, we observed that constructing the cytosolic biosynthesis pathway resulted in compromised fatty alcohol production in the methylotrophic yeast Ogataea polymorpha. Alternatively, peroxisomal coupling of fatty alcohol biosynthesis and methanol utilization significantly improved fatty alcohol production by 3.9-fold. Enhancing the supply of precursor fatty acyl-CoA and cofactor NADPH in the peroxisomes by global metabolic rewiring further improved fatty alcohol production by 2.5-fold and produced 3.6 g/L fatty alcohols from methanol under fed-batch fermentation. We demonstrated that peroxisome compartmentalization is helpful for coupling methanol utilization and product synthesis, and with this approach, constructing efficient microbial cell factories for methanol biotransformation is feasible.
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spelling pubmed-100410952023-09-13 Peroxisomal metabolic coupling improves fatty alcohol production from sole methanol in yeast Zhai, Xiaoxin Gao, Jiaoqi Li, Yunxia Grininger, Martin Zhou, Yongjin J. Proc Natl Acad Sci U S A Biological Sciences Methanol is an ideal feedstock for chemical and biological manufacturing. Constructing an efficient cell factory is essential for producing complex compounds through methanol biotransformation, in which coordinating methanol use and product synthesis is often necessary. In methylotrophic yeast, methanol utilization mainly occurs in peroxisomes, which creates challenges in driving the metabolic flux toward product biosynthesis. Here, we observed that constructing the cytosolic biosynthesis pathway resulted in compromised fatty alcohol production in the methylotrophic yeast Ogataea polymorpha. Alternatively, peroxisomal coupling of fatty alcohol biosynthesis and methanol utilization significantly improved fatty alcohol production by 3.9-fold. Enhancing the supply of precursor fatty acyl-CoA and cofactor NADPH in the peroxisomes by global metabolic rewiring further improved fatty alcohol production by 2.5-fold and produced 3.6 g/L fatty alcohols from methanol under fed-batch fermentation. We demonstrated that peroxisome compartmentalization is helpful for coupling methanol utilization and product synthesis, and with this approach, constructing efficient microbial cell factories for methanol biotransformation is feasible. National Academy of Sciences 2023-03-13 2023-03-21 /pmc/articles/PMC10041095/ /pubmed/36913588 http://dx.doi.org/10.1073/pnas.2220816120 Text en Copyright © 2023 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/This article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Biological Sciences
Zhai, Xiaoxin
Gao, Jiaoqi
Li, Yunxia
Grininger, Martin
Zhou, Yongjin J.
Peroxisomal metabolic coupling improves fatty alcohol production from sole methanol in yeast
title Peroxisomal metabolic coupling improves fatty alcohol production from sole methanol in yeast
title_full Peroxisomal metabolic coupling improves fatty alcohol production from sole methanol in yeast
title_fullStr Peroxisomal metabolic coupling improves fatty alcohol production from sole methanol in yeast
title_full_unstemmed Peroxisomal metabolic coupling improves fatty alcohol production from sole methanol in yeast
title_short Peroxisomal metabolic coupling improves fatty alcohol production from sole methanol in yeast
title_sort peroxisomal metabolic coupling improves fatty alcohol production from sole methanol in yeast
topic Biological Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10041095/
https://www.ncbi.nlm.nih.gov/pubmed/36913588
http://dx.doi.org/10.1073/pnas.2220816120
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