Two-step pathway for isoprenoid synthesis
© 2018 National Academy of Sciences. All rights reserved. Isoprenoids comprise a large class of chemicals of significant interest due to their diverse properties. Biological production of isoprenoids is considered to be the most efficient way for their large-scale production. Isoprenoid biosynthesis...
| Main Authors: | , , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | English |
| Published: |
Proceedings of the National Academy of Sciences
2021
|
| Online Access: | https://hdl.handle.net/1721.1/135157 |
| _version_ | 1811080004073684992 |
|---|---|
| author | Chatzivasileiou, Alkiviadis Orfefs Ward, Valerie Edgar, Steven McBride Stephanopoulos, Gregory |
| author2 | Massachusetts Institute of Technology. Department of Chemical Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Chemical Engineering Chatzivasileiou, Alkiviadis Orfefs Ward, Valerie Edgar, Steven McBride Stephanopoulos, Gregory |
| author_sort | Chatzivasileiou, Alkiviadis Orfefs |
| collection | MIT |
| description | © 2018 National Academy of Sciences. All rights reserved. Isoprenoids comprise a large class of chemicals of significant interest due to their diverse properties. Biological production of isoprenoids is considered to be the most efficient way for their large-scale production. Isoprenoid biosynthesis has thus far been dependent on pathways inextricably linked to glucose metabolism. These pathways suffer from inherent limitations due to their length, complex regulation, and extensive cofactor requirements. Here, we present a synthetic isoprenoid pathway that aims to overcome these limitations. This isopentenol utilization pathway (IUP) can produce isopentenyl diphosphate or dimethylallyl diphosphate, the main precursors to isoprenoid synthesis, through sequential phosphorylation of isopentenol isomers isoprenol or prenol. After identifying suitable enzymes and constructing the pathway, we attempted to probe the limits of the IUP for producing various isoprenoid downstream products. The IUP flux exceeded the capacity of almost all downstream pathways tested and was competitive with the highest isoprenoid fluxes reported. |
| first_indexed | 2024-09-23T11:23:59Z |
| format | Article |
| id | mit-1721.1/135157 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T11:23:59Z |
| publishDate | 2021 |
| publisher | Proceedings of the National Academy of Sciences |
| record_format | dspace |
| spelling | mit-1721.1/1351572023-03-01T15:10:36Z Two-step pathway for isoprenoid synthesis Chatzivasileiou, Alkiviadis Orfefs Ward, Valerie Edgar, Steven McBride Stephanopoulos, Gregory Massachusetts Institute of Technology. Department of Chemical Engineering © 2018 National Academy of Sciences. All rights reserved. Isoprenoids comprise a large class of chemicals of significant interest due to their diverse properties. Biological production of isoprenoids is considered to be the most efficient way for their large-scale production. Isoprenoid biosynthesis has thus far been dependent on pathways inextricably linked to glucose metabolism. These pathways suffer from inherent limitations due to their length, complex regulation, and extensive cofactor requirements. Here, we present a synthetic isoprenoid pathway that aims to overcome these limitations. This isopentenol utilization pathway (IUP) can produce isopentenyl diphosphate or dimethylallyl diphosphate, the main precursors to isoprenoid synthesis, through sequential phosphorylation of isopentenol isomers isoprenol or prenol. After identifying suitable enzymes and constructing the pathway, we attempted to probe the limits of the IUP for producing various isoprenoid downstream products. The IUP flux exceeded the capacity of almost all downstream pathways tested and was competitive with the highest isoprenoid fluxes reported. 2021-10-27T20:11:00Z 2021-10-27T20:11:00Z 2019 2019-09-16T14:45:19Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/135157 en 10.1073/PNAS.1812935116 Proceedings of the National Academy of Sciences of the United States of America 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 Proceedings of the National Academy of Sciences PNAS |
| spellingShingle | Chatzivasileiou, Alkiviadis Orfefs Ward, Valerie Edgar, Steven McBride Stephanopoulos, Gregory Two-step pathway for isoprenoid synthesis |
| title | Two-step pathway for isoprenoid synthesis |
| title_full | Two-step pathway for isoprenoid synthesis |
| title_fullStr | Two-step pathway for isoprenoid synthesis |
| title_full_unstemmed | Two-step pathway for isoprenoid synthesis |
| title_short | Two-step pathway for isoprenoid synthesis |
| title_sort | two step pathway for isoprenoid synthesis |
| url | https://hdl.handle.net/1721.1/135157 |
| work_keys_str_mv | AT chatzivasileioualkiviadisorfefs twosteppathwayforisoprenoidsynthesis AT wardvalerie twosteppathwayforisoprenoidsynthesis AT edgarstevenmcbride twosteppathwayforisoprenoidsynthesis AT stephanopoulosgregory twosteppathwayforisoprenoidsynthesis |