Compartmentalization of metabolic pathways in yeast mitochondria improves the production of branched-chain alcohols
Efforts to improve the production of a compound of interest in Saccharomyces cerevisiae have mainly involved engineering or overexpression of cytoplasmic enzymes. We show that targeting metabolic pathways to mitochondria can increase production compared with overexpression of the enzymes involved in...
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| Format: | Article |
| Language: | en_US |
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Nature Publishing Group
2014
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| Online Access: | http://hdl.handle.net/1721.1/84595 https://orcid.org/0000-0003-3704-2899 https://orcid.org/0000-0001-6909-4568 |
| _version_ | 1826195399887552512 |
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| author | Stephanopoulos, Gregory Avalos, Jose L. Fink, Gerald R. |
| author2 | Massachusetts Institute of Technology. Department of Chemical Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Chemical Engineering Stephanopoulos, Gregory Avalos, Jose L. Fink, Gerald R. |
| author_sort | Stephanopoulos, Gregory |
| collection | MIT |
| description | Efforts to improve the production of a compound of interest in Saccharomyces cerevisiae have mainly involved engineering or overexpression of cytoplasmic enzymes. We show that targeting metabolic pathways to mitochondria can increase production compared with overexpression of the enzymes involved in the same pathways in the cytoplasm. Compartmentalization of the Ehrlich pathway into mitochondria increased isobutanol production by 260%, whereas overexpression of the same pathway in the cytoplasm only improved yields by 10%, compared with a strain overproducing enzymes involved in only the first three steps of the biosynthetic pathway. Subcellular fractionation of engineered strains revealed that targeting the enzymes of the Ehrlich pathway to the mitochondria achieves greater local enzyme concentrations. Other benefits of compartmentalization may include increased availability of intermediates, removing the need to transport intermediates out of the mitochondrion and reducing the loss of intermediates to competing pathways. |
| first_indexed | 2024-09-23T10:12:04Z |
| format | Article |
| id | mit-1721.1/84595 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T10:12:04Z |
| publishDate | 2014 |
| publisher | Nature Publishing Group |
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| spelling | mit-1721.1/845952022-09-30T19:33:27Z Compartmentalization of metabolic pathways in yeast mitochondria improves the production of branched-chain alcohols Stephanopoulos, Gregory Avalos, Jose L. Fink, Gerald R. Massachusetts Institute of Technology. Department of Chemical Engineering Whitehead Institute for Biomedical Research Avalos, Jose L. Stephanopoulos, Gregory Fink, Gerald R. Efforts to improve the production of a compound of interest in Saccharomyces cerevisiae have mainly involved engineering or overexpression of cytoplasmic enzymes. We show that targeting metabolic pathways to mitochondria can increase production compared with overexpression of the enzymes involved in the same pathways in the cytoplasm. Compartmentalization of the Ehrlich pathway into mitochondria increased isobutanol production by 260%, whereas overexpression of the same pathway in the cytoplasm only improved yields by 10%, compared with a strain overproducing enzymes involved in only the first three steps of the biosynthetic pathway. Subcellular fractionation of engineered strains revealed that targeting the enzymes of the Ehrlich pathway to the mitochondria achieves greater local enzyme concentrations. Other benefits of compartmentalization may include increased availability of intermediates, removing the need to transport intermediates out of the mitochondrion and reducing the loss of intermediates to competing pathways. National Institutes of Health (U.S.). Ruth L. Kirschstein National Research Service Award (1F32GM098022-01A1) National Institutes of Health (U.S.) (Grant GM040266) Shell Global Solutions (US) 2014-01-27T19:03:29Z 2014-01-27T19:03:29Z 2013-02 2012-11 Article http://purl.org/eprint/type/JournalArticle 1087-0156 1546-1696 http://hdl.handle.net/1721.1/84595 Avalos, José L, Gerald R Fink, and Gregory Stephanopoulos. “Compartmentalization of metabolic pathways in yeast mitochondria improves the production of branched-chain alcohols.” Nature Biotechnology 31, no. 4 (February 17, 2013): 335-341. https://orcid.org/0000-0003-3704-2899 https://orcid.org/0000-0001-6909-4568 en_US http://dx.doi.org/10.1038/nbt.2509 Nature Biotechnology Creative Commons Attribution-Noncommercial-Share Alike 3.0 http://creativecommons.org/licenses/by-nc-sa/3.0/ application/pdf Nature Publishing Group PMC |
| spellingShingle | Stephanopoulos, Gregory Avalos, Jose L. Fink, Gerald R. Compartmentalization of metabolic pathways in yeast mitochondria improves the production of branched-chain alcohols |
| title | Compartmentalization of metabolic pathways in yeast mitochondria improves the production of branched-chain alcohols |
| title_full | Compartmentalization of metabolic pathways in yeast mitochondria improves the production of branched-chain alcohols |
| title_fullStr | Compartmentalization of metabolic pathways in yeast mitochondria improves the production of branched-chain alcohols |
| title_full_unstemmed | Compartmentalization of metabolic pathways in yeast mitochondria improves the production of branched-chain alcohols |
| title_short | Compartmentalization of metabolic pathways in yeast mitochondria improves the production of branched-chain alcohols |
| title_sort | compartmentalization of metabolic pathways in yeast mitochondria improves the production of branched chain alcohols |
| url | http://hdl.handle.net/1721.1/84595 https://orcid.org/0000-0003-3704-2899 https://orcid.org/0000-0001-6909-4568 |
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