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Title: Optimization of the IPP-bypass mevalonate pathway and fed-batch fermentation for the production of isoprenol in Escherichia coli

Abstract

Isoprenol (3-methyl-3-buten-1-ol) is a drop-in biofuel and a precursor for commodity chemicals. Biological production of isoprenol via the mevalonate pathway has been developed and optimized extensively in Escherichia coli, but high ATP requirements and isopentenyl diphosphate (IPP) toxicity have made it difficult to achieve high titer, yield, and large-scale production. To overcome these limitations, an IPP-bypass pathway was previously developed using the promiscuous activity of diphosphomevalonate decarboxylase, and enabled the production of isoprenol at a comparable yield and titer to the original pathway. In this study, we optimized this pathway, substantially improving isoprenol production. A titer of 3.7 g/L (0.14 g isoprenol per g glucose) was achieved in batch conditions using minimal medium by pathway optimization, and a further optimization of the fed-batch fermentation process enabled an isoprenol titer of 10.8 g/L (yield of 0.105 g/g and maximum productivity of 0.157 g L -1 h -1), which is the highest reported titer for this compound. The substantial increase in isoprenol titer via the IPP-bypass pathway in this study will facilitate progress toward commercialization.

Authors:
; ; ; ; ; ; ; ; ;
Publication Date:
Research Org.:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org.:
USDOE Office of Science (SC)
OSTI Identifier:
1582046
Alternate Identifier(s):
OSTI ID: 1565999
Grant/Contract Number:  
AC02-05CH11231
Resource Type:
Accepted Manuscript
Journal Name:
Metabolic Engineering
Additional Journal Information:
Journal Volume: 56; Journal Issue: C; Journal ID: ISSN 1096-7176
Publisher:
Elsevier
Country of Publication:
United States
Language:
English

Citation Formats

Kang, Aram, Mendez-Perez, Daniel, Goh, Ee-Been, Baidoo, Edward E. K., Benites, Veronica T., Beller, Harry R., Keasling, Jay D., Adams, Paul D., Mukhopadhyay, Aindrila, and Lee, Taek Soon. Optimization of the IPP-bypass mevalonate pathway and fed-batch fermentation for the production of isoprenol in Escherichia coli. United States: N. p., 2019. Web. doi:10.1016/j.ymben.2019.09.003.
Kang, Aram, Mendez-Perez, Daniel, Goh, Ee-Been, Baidoo, Edward E. K., Benites, Veronica T., Beller, Harry R., Keasling, Jay D., Adams, Paul D., Mukhopadhyay, Aindrila, & Lee, Taek Soon. Optimization of the IPP-bypass mevalonate pathway and fed-batch fermentation for the production of isoprenol in Escherichia coli. United States. doi:10.1016/j.ymben.2019.09.003.
Kang, Aram, Mendez-Perez, Daniel, Goh, Ee-Been, Baidoo, Edward E. K., Benites, Veronica T., Beller, Harry R., Keasling, Jay D., Adams, Paul D., Mukhopadhyay, Aindrila, and Lee, Taek Soon. Sun . "Optimization of the IPP-bypass mevalonate pathway and fed-batch fermentation for the production of isoprenol in Escherichia coli". United States. doi:10.1016/j.ymben.2019.09.003.
@article{osti_1582046,
title = {Optimization of the IPP-bypass mevalonate pathway and fed-batch fermentation for the production of isoprenol in Escherichia coli},
author = {Kang, Aram and Mendez-Perez, Daniel and Goh, Ee-Been and Baidoo, Edward E. K. and Benites, Veronica T. and Beller, Harry R. and Keasling, Jay D. and Adams, Paul D. and Mukhopadhyay, Aindrila and Lee, Taek Soon},
abstractNote = {Isoprenol (3-methyl-3-buten-1-ol) is a drop-in biofuel and a precursor for commodity chemicals. Biological production of isoprenol via the mevalonate pathway has been developed and optimized extensively in Escherichia coli, but high ATP requirements and isopentenyl diphosphate (IPP) toxicity have made it difficult to achieve high titer, yield, and large-scale production. To overcome these limitations, an IPP-bypass pathway was previously developed using the promiscuous activity of diphosphomevalonate decarboxylase, and enabled the production of isoprenol at a comparable yield and titer to the original pathway. In this study, we optimized this pathway, substantially improving isoprenol production. A titer of 3.7 g/L (0.14 g isoprenol per g glucose) was achieved in batch conditions using minimal medium by pathway optimization, and a further optimization of the fed-batch fermentation process enabled an isoprenol titer of 10.8 g/L (yield of 0.105 g/g and maximum productivity of 0.157 g L-1 h-1), which is the highest reported titer for this compound. The substantial increase in isoprenol titer via the IPP-bypass pathway in this study will facilitate progress toward commercialization.},
doi = {10.1016/j.ymben.2019.09.003},
journal = {Metabolic Engineering},
number = C,
volume = 56,
place = {United States},
year = {2019},
month = {12}
}

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