A platform pathway for production of 3-hydroxyacids provides a biosynthetic route to 3-hydroxy-γ-butyrolactone
The replacement of petroleum feedstocks with biomass to produce platform chemicals requires the development of appropriate conversion technologies. 3-Hydroxy-γ-butyrolactone has been identified as one such chemical; however, there are no naturally occurring biosynthetic pathways for this molecule or...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | en_US |
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Nature Publishing Group
2013
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| Online Access: | http://hdl.handle.net/1721.1/79823 https://orcid.org/0000-0003-0437-3157 https://orcid.org/0000-0002-4908-3914 |
| _version_ | 1826200949135245312 |
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| author | Martin, Collin H. Dhamankar, Himanshu Hemant Tseng, Hsien-Chung Sheppard, Micah James Reisch, Christopher R. Prather, Kristala L. Jones |
| author2 | Massachusetts Institute of Technology. Department of Chemical Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Chemical Engineering Martin, Collin H. Dhamankar, Himanshu Hemant Tseng, Hsien-Chung Sheppard, Micah James Reisch, Christopher R. Prather, Kristala L. Jones |
| author_sort | Martin, Collin H. |
| collection | MIT |
| description | The replacement of petroleum feedstocks with biomass to produce platform chemicals requires the development of appropriate conversion technologies. 3-Hydroxy-γ-butyrolactone has been identified as one such chemical; however, there are no naturally occurring biosynthetic pathways for this molecule or its hydrolyzed form, 3,4-dihydroxybutyric acid. Here we design a novel pathway to produce various chiral 3-hydroxyacids, including 3,4-dihydroxybutyric acid, consisting of enzymes that condense two acyl-CoAs, stereospecifically reduce the resulting β-ketone and hydrolyze the CoA thioester to release the free acid. Acetyl-CoA serves as one substrate for the condensation reaction, whereas the second is produced intracellularly by a pathway enzyme that converts exogenously supplied organic acids. Feeding of butyrate, isobutyrate and glycolate results in the production of 3-hydroxyhexanoate, 3-hydroxy-4-methylvalerate and 3,4-dihydroxybutyric acid+3-hydroxy-γ-butyrolactone, respectively, molecules with potential uses in applications from materials to medicines. We also unexpectedly observe the condensation reaction resulting in the production of the 2,3-dihydroxybutyric acid isomer, a potential value-added monomer. |
| first_indexed | 2024-09-23T11:44:15Z |
| format | Article |
| id | mit-1721.1/79823 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T11:44:15Z |
| publishDate | 2013 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/798232022-10-01T05:37:01Z A platform pathway for production of 3-hydroxyacids provides a biosynthetic route to 3-hydroxy-γ-butyrolactone Martin, Collin H. Dhamankar, Himanshu Hemant Tseng, Hsien-Chung Sheppard, Micah James Reisch, Christopher R. Prather, Kristala L. Jones Massachusetts Institute of Technology. Department of Chemical Engineering Massachusetts Institute of Technology. Synthetic Biology Center Prather, Kristala L. Jones Martin, Collin H. Dhamankar, Himanshu Hemant Tseng, Hsien-Chung Sheppard, Micah James Reisch, Christopher R. Prather, Kristala L. Jones The replacement of petroleum feedstocks with biomass to produce platform chemicals requires the development of appropriate conversion technologies. 3-Hydroxy-γ-butyrolactone has been identified as one such chemical; however, there are no naturally occurring biosynthetic pathways for this molecule or its hydrolyzed form, 3,4-dihydroxybutyric acid. Here we design a novel pathway to produce various chiral 3-hydroxyacids, including 3,4-dihydroxybutyric acid, consisting of enzymes that condense two acyl-CoAs, stereospecifically reduce the resulting β-ketone and hydrolyze the CoA thioester to release the free acid. Acetyl-CoA serves as one substrate for the condensation reaction, whereas the second is produced intracellularly by a pathway enzyme that converts exogenously supplied organic acids. Feeding of butyrate, isobutyrate and glycolate results in the production of 3-hydroxyhexanoate, 3-hydroxy-4-methylvalerate and 3,4-dihydroxybutyric acid+3-hydroxy-γ-butyrolactone, respectively, molecules with potential uses in applications from materials to medicines. We also unexpectedly observe the condensation reaction resulting in the production of the 2,3-dihydroxybutyric acid isomer, a potential value-added monomer. 2013-08-09T15:28:32Z 2013-08-09T15:28:32Z 2013-01 2012-10 Article http://purl.org/eprint/type/JournalArticle 2041-1723 http://hdl.handle.net/1721.1/79823 Martin, Collin H., Himanshu Dhamankar, Hsien-Chung Tseng, et al. 2013 A Platform Pathway for Production of 3-hydroxyacids Provides a Biosynthetic Route to 3-hydroxy-γ-butyrolactone. Nature Communications 4: 1414. 1-10. https://orcid.org/0000-0003-0437-3157 https://orcid.org/0000-0002-4908-3914 en_US http://dx.doi.org/10.1038/ncomms2418 Nature Communications Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Nature Publishing Group Prof. Prather via Erja Kajosalo |
| spellingShingle | Martin, Collin H. Dhamankar, Himanshu Hemant Tseng, Hsien-Chung Sheppard, Micah James Reisch, Christopher R. Prather, Kristala L. Jones A platform pathway for production of 3-hydroxyacids provides a biosynthetic route to 3-hydroxy-γ-butyrolactone |
| title | A platform pathway for production of 3-hydroxyacids provides a biosynthetic route to 3-hydroxy-γ-butyrolactone |
| title_full | A platform pathway for production of 3-hydroxyacids provides a biosynthetic route to 3-hydroxy-γ-butyrolactone |
| title_fullStr | A platform pathway for production of 3-hydroxyacids provides a biosynthetic route to 3-hydroxy-γ-butyrolactone |
| title_full_unstemmed | A platform pathway for production of 3-hydroxyacids provides a biosynthetic route to 3-hydroxy-γ-butyrolactone |
| title_short | A platform pathway for production of 3-hydroxyacids provides a biosynthetic route to 3-hydroxy-γ-butyrolactone |
| title_sort | platform pathway for production of 3 hydroxyacids provides a biosynthetic route to 3 hydroxy γ butyrolactone |
| url | http://hdl.handle.net/1721.1/79823 https://orcid.org/0000-0003-0437-3157 https://orcid.org/0000-0002-4908-3914 |
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