Yarrowia lipolytica chassis strains engineered to produce aromatic amino acids via the shikimate pathway

Summary Yarrowia lipolytica is widely used as a microbial producer of lipids and lipid derivatives. Here, we exploited this yeast’s potential to generate aromatic amino acids by developing chassis strains optimized for the production of phenylalanine, tyrosine and tryptophan. We engineered the shiki...

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Autores principales: Macarena Larroude, Jean‐Marc Nicaud, Tristan Rossignol
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Publicado: Wiley 2021
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Acceso en línea:https://doaj.org/article/1ef1f38c80f84c65a9b53173b0f16ac4
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spelling oai:doaj.org-article:1ef1f38c80f84c65a9b53173b0f16ac42021-11-18T15:39:52ZYarrowia lipolytica chassis strains engineered to produce aromatic amino acids via the shikimate pathway1751-791510.1111/1751-7915.13745https://doaj.org/article/1ef1f38c80f84c65a9b53173b0f16ac42021-11-01T00:00:00Zhttps://doi.org/10.1111/1751-7915.13745https://doaj.org/toc/1751-7915Summary Yarrowia lipolytica is widely used as a microbial producer of lipids and lipid derivatives. Here, we exploited this yeast’s potential to generate aromatic amino acids by developing chassis strains optimized for the production of phenylalanine, tyrosine and tryptophan. We engineered the shikimate pathway to overexpress a combination of Y. lipolytica and heterologous feedback‐insensitive enzyme variants. Our best chassis strain displayed high levels of de novo Ehrlich metabolite production (up to 0.14 g l−1 in minimal growth medium), which represented a 93‐fold increase compared to the wild‐type strain (0.0015 g l−1). Production was further boosted to 0.48 g l−1 when glycerol, a low‐cost carbon source, was used, concomitantly to high secretion of phenylalanine precursor (1 g l−1). Among these metabolites, 2‐phenylethanol is of particular interest due to its rose‐like flavour. We also established a production pathway for generating protodeoxyviolaceinic acid, a dye derived from tryptophan, in a chassis strain optimized for chorismate, the precursor of tryptophan. We have thus demonstrated that Y. lipolytica can serve as a platform for the sustainable de novo bio‐production of high‐value aromatic compounds, and we have greatly improved our understanding of the potential feedback‐based regulation of the shikimate pathway in this yeast.Macarena LarroudeJean‐Marc NicaudTristan RossignolWileyarticleBiotechnologyTP248.13-248.65ENMicrobial Biotechnology, Vol 14, Iss 6, Pp 2420-2434 (2021)
institution DOAJ
collection DOAJ
language EN
topic Biotechnology
TP248.13-248.65
spellingShingle Biotechnology
TP248.13-248.65
Macarena Larroude
Jean‐Marc Nicaud
Tristan Rossignol
Yarrowia lipolytica chassis strains engineered to produce aromatic amino acids via the shikimate pathway
description Summary Yarrowia lipolytica is widely used as a microbial producer of lipids and lipid derivatives. Here, we exploited this yeast’s potential to generate aromatic amino acids by developing chassis strains optimized for the production of phenylalanine, tyrosine and tryptophan. We engineered the shikimate pathway to overexpress a combination of Y. lipolytica and heterologous feedback‐insensitive enzyme variants. Our best chassis strain displayed high levels of de novo Ehrlich metabolite production (up to 0.14 g l−1 in minimal growth medium), which represented a 93‐fold increase compared to the wild‐type strain (0.0015 g l−1). Production was further boosted to 0.48 g l−1 when glycerol, a low‐cost carbon source, was used, concomitantly to high secretion of phenylalanine precursor (1 g l−1). Among these metabolites, 2‐phenylethanol is of particular interest due to its rose‐like flavour. We also established a production pathway for generating protodeoxyviolaceinic acid, a dye derived from tryptophan, in a chassis strain optimized for chorismate, the precursor of tryptophan. We have thus demonstrated that Y. lipolytica can serve as a platform for the sustainable de novo bio‐production of high‐value aromatic compounds, and we have greatly improved our understanding of the potential feedback‐based regulation of the shikimate pathway in this yeast.
format article
author Macarena Larroude
Jean‐Marc Nicaud
Tristan Rossignol
author_facet Macarena Larroude
Jean‐Marc Nicaud
Tristan Rossignol
author_sort Macarena Larroude
title Yarrowia lipolytica chassis strains engineered to produce aromatic amino acids via the shikimate pathway
title_short Yarrowia lipolytica chassis strains engineered to produce aromatic amino acids via the shikimate pathway
title_full Yarrowia lipolytica chassis strains engineered to produce aromatic amino acids via the shikimate pathway
title_fullStr Yarrowia lipolytica chassis strains engineered to produce aromatic amino acids via the shikimate pathway
title_full_unstemmed Yarrowia lipolytica chassis strains engineered to produce aromatic amino acids via the shikimate pathway
title_sort yarrowia lipolytica chassis strains engineered to produce aromatic amino acids via the shikimate pathway
publisher Wiley
publishDate 2021
url https://doaj.org/article/1ef1f38c80f84c65a9b53173b0f16ac4
work_keys_str_mv AT macarenalarroude yarrowialipolyticachassisstrainsengineeredtoproducearomaticaminoacidsviatheshikimatepathway
AT jeanmarcnicaud yarrowialipolyticachassisstrainsengineeredtoproducearomaticaminoacidsviatheshikimatepathway
AT tristanrossignol yarrowialipolyticachassisstrainsengineeredtoproducearomaticaminoacidsviatheshikimatepathway
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