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Title: Two-step pathway for isoprenoid synthesis

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.
Authors:
ORCiD logo ; ; ;
Publication Date:
Grant/Contract Number:
SC 000 8744; EE 000 7531
Type:
Published Article
Journal Name:
Proceedings of the National Academy of Sciences of the United States of America
Additional Journal Information:
Journal Name: Proceedings of the National Academy of Sciences of the United States of America Journal Volume: 116 Journal Issue: 2; Journal ID: ISSN 0027-8424
Publisher:
Proceedings of the National Academy of Sciences
Sponsoring Org:
USDOE
Country of Publication:
United States
Language:
English
OSTI Identifier:
1488765

Chatzivasileiou, Alkiviadis Orfefs, Ward, Valerie, Edgar, Steven McBride, and Stephanopoulos, Gregory. Two-step pathway for isoprenoid synthesis. United States: N. p., Web. doi:10.1073/pnas.1812935116.
Chatzivasileiou, Alkiviadis Orfefs, Ward, Valerie, Edgar, Steven McBride, & Stephanopoulos, Gregory. Two-step pathway for isoprenoid synthesis. United States. doi:10.1073/pnas.1812935116.
Chatzivasileiou, Alkiviadis Orfefs, Ward, Valerie, Edgar, Steven McBride, and Stephanopoulos, Gregory. 2018. "Two-step pathway for isoprenoid synthesis". United States. doi:10.1073/pnas.1812935116.
@article{osti_1488765,
title = {Two-step pathway for isoprenoid synthesis},
author = {Chatzivasileiou, Alkiviadis Orfefs and Ward, Valerie and Edgar, Steven McBride and Stephanopoulos, Gregory},
abstractNote = {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.},
doi = {10.1073/pnas.1812935116},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
number = 2,
volume = 116,
place = {United States},
year = {2018},
month = {12}
}

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