Transforming yeast peroxisomes into microfactories for the efficient production of high-value isoprenoids

Research output: Contribution to journal › Journal article › Research › peer-review

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Transforming yeast peroxisomes into microfactories for the efficient production of high-value isoprenoids. / Dusséaux, Simon; Wajn, William Thomas; Liu, Yixuan; Ignea, Codruta; Kampranis, Sotirios C.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 117, No. 50, 2020, p. 31789-31799.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Dusséaux, S, Wajn, WT, Liu, Y, Ignea, C & Kampranis, SC 2020, 'Transforming yeast peroxisomes into microfactories for the efficient production of high-value isoprenoids', Proceedings of the National Academy of Sciences of the United States of America, vol. 117, no. 50, pp. 31789-31799. https://doi.org/10.1073/pnas.2013968117

APA

Dusséaux, S., Wajn, W. T., Liu, Y., Ignea, C., & Kampranis, S. C. (2020). Transforming yeast peroxisomes into microfactories for the efficient production of high-value isoprenoids. Proceedings of the National Academy of Sciences of the United States of America, 117(50), 31789-31799. https://doi.org/10.1073/pnas.2013968117

Vancouver

Dusséaux S, Wajn WT, Liu Y, Ignea C, Kampranis SC. Transforming yeast peroxisomes into microfactories for the efficient production of high-value isoprenoids. Proceedings of the National Academy of Sciences of the United States of America. 2020;117(50):31789-31799. https://doi.org/10.1073/pnas.2013968117

Author

Dusséaux, Simon ; Wajn, William Thomas ; Liu, Yixuan ; Ignea, Codruta ; Kampranis, Sotirios C. / Transforming yeast peroxisomes into microfactories for the efficient production of high-value isoprenoids. In: Proceedings of the National Academy of Sciences of the United States of America. 2020 ; Vol. 117, No. 50. pp. 31789-31799.

Bibtex

@article{5fad065a92d540cea94b8ad71e051e1d,
title = "Transforming yeast peroxisomes into microfactories for the efficient production of high-value isoprenoids",
abstract = "Current approaches for the production of high-value compounds in microorganisms mostly use the cytosol as a general reaction vessel. However, competing pathways and metabolic cross-talk frequently prevent efficient synthesis of target compounds in the cytosol. Eukaryotic cells control the complexity of their metabolism by harnessing organelles to insulate biochemical pathways. Inspired by this concept, herein we transform yeast peroxisomes into microfactories for geranyl diphosphate-derived compounds, focusing on monoterpenoids, monoterpene indole alkaloids, and cannabinoids. We introduce a complete mevalonate pathway in the peroxisome to convert acetyl-CoA to several commercially important monoterpenes and achieve up to 125-fold increase over cytosolic production. Furthermore, peroxisomal production improves subsequent decoration by cytochrome P450s, supporting efficient conversion of (S)-(-)-limonene to the menthol precursor trans-isopiperitenol. We also establish synthesis of 8-hydroxygeraniol, the precursor of monoterpene indole alkaloids, and cannabigerolic acid, the cannabinoid precursor. Our findings establish peroxisomal engineering as an efficient strategy for the production of isoprenoids.",
keywords = "Compartmentalization, Metabolic engineering, Mevalonate pathway, Synthetic biology, Terpenoid",
author = "Simon Duss{\'e}aux and Wajn, {William Thomas} and Yixuan Liu and Codruta Ignea and Kampranis, {Sotirios C.}",
year = "2020",
doi = "10.1073/pnas.2013968117",
language = "English",
volume = "117",
pages = "31789--31799",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
publisher = "The National Academy of Sciences of the United States of America",
number = "50",

}

RIS

TY - JOUR

T1 - Transforming yeast peroxisomes into microfactories for the efficient production of high-value isoprenoids

AU - Dusséaux, Simon

AU - Wajn, William Thomas

AU - Liu, Yixuan

AU - Ignea, Codruta

AU - Kampranis, Sotirios C.

PY - 2020

Y1 - 2020

N2 - Current approaches for the production of high-value compounds in microorganisms mostly use the cytosol as a general reaction vessel. However, competing pathways and metabolic cross-talk frequently prevent efficient synthesis of target compounds in the cytosol. Eukaryotic cells control the complexity of their metabolism by harnessing organelles to insulate biochemical pathways. Inspired by this concept, herein we transform yeast peroxisomes into microfactories for geranyl diphosphate-derived compounds, focusing on monoterpenoids, monoterpene indole alkaloids, and cannabinoids. We introduce a complete mevalonate pathway in the peroxisome to convert acetyl-CoA to several commercially important monoterpenes and achieve up to 125-fold increase over cytosolic production. Furthermore, peroxisomal production improves subsequent decoration by cytochrome P450s, supporting efficient conversion of (S)-(-)-limonene to the menthol precursor trans-isopiperitenol. We also establish synthesis of 8-hydroxygeraniol, the precursor of monoterpene indole alkaloids, and cannabigerolic acid, the cannabinoid precursor. Our findings establish peroxisomal engineering as an efficient strategy for the production of isoprenoids.

AB - Current approaches for the production of high-value compounds in microorganisms mostly use the cytosol as a general reaction vessel. However, competing pathways and metabolic cross-talk frequently prevent efficient synthesis of target compounds in the cytosol. Eukaryotic cells control the complexity of their metabolism by harnessing organelles to insulate biochemical pathways. Inspired by this concept, herein we transform yeast peroxisomes into microfactories for geranyl diphosphate-derived compounds, focusing on monoterpenoids, monoterpene indole alkaloids, and cannabinoids. We introduce a complete mevalonate pathway in the peroxisome to convert acetyl-CoA to several commercially important monoterpenes and achieve up to 125-fold increase over cytosolic production. Furthermore, peroxisomal production improves subsequent decoration by cytochrome P450s, supporting efficient conversion of (S)-(-)-limonene to the menthol precursor trans-isopiperitenol. We also establish synthesis of 8-hydroxygeraniol, the precursor of monoterpene indole alkaloids, and cannabigerolic acid, the cannabinoid precursor. Our findings establish peroxisomal engineering as an efficient strategy for the production of isoprenoids.

KW - Compartmentalization

KW - Metabolic engineering

KW - Mevalonate pathway

KW - Synthetic biology

KW - Terpenoid

U2 - 10.1073/pnas.2013968117

DO - 10.1073/pnas.2013968117

M3 - Journal article

C2 - 33268495

AN - SCOPUS:85098470581

VL - 117

SP - 31789

EP - 31799

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 50

ER -

ID: 255786672