Correlation analysis of targeted proteins and metabolites to assess and engineer microbial isopentenol production

Research output: Contribution to journal › Journal article › Research › peer-review

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Correlation analysis of targeted proteins and metabolites to assess and engineer microbial isopentenol production. / George, Kevin W; Chen, Amy; Jain, Aakriti; Batth, Tanveer S; Baidoo, Edward E K; Wang, George; Adams, Paul D; Petzold, Christopher J; Keasling, Jay D; Lee, Taek Soon.

In: Biotechnology and Bioengineering, Vol. 111, No. 8, 2014, p. 1648-1658.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

George, KW, Chen, A, Jain, A, Batth, TS, Baidoo, EEK, Wang, G, Adams, PD, Petzold, CJ, Keasling, JD & Lee, TS 2014, 'Correlation analysis of targeted proteins and metabolites to assess and engineer microbial isopentenol production', Biotechnology and Bioengineering, vol. 111, no. 8, pp. 1648-1658. https://doi.org/10.1002/bit.25226

APA

George, K. W., Chen, A., Jain, A., Batth, T. S., Baidoo, E. E. K., Wang, G., Adams, P. D., Petzold, C. J., Keasling, J. D., & Lee, T. S. (2014). Correlation analysis of targeted proteins and metabolites to assess and engineer microbial isopentenol production. Biotechnology and Bioengineering, 111(8), 1648-1658. https://doi.org/10.1002/bit.25226

Vancouver

George KW, Chen A, Jain A, Batth TS, Baidoo EEK, Wang G et al. Correlation analysis of targeted proteins and metabolites to assess and engineer microbial isopentenol production. Biotechnology and Bioengineering. 2014;111(8):1648-1658. https://doi.org/10.1002/bit.25226

Author

George, Kevin W ; Chen, Amy ; Jain, Aakriti ; Batth, Tanveer S ; Baidoo, Edward E K ; Wang, George ; Adams, Paul D ; Petzold, Christopher J ; Keasling, Jay D ; Lee, Taek Soon. / Correlation analysis of targeted proteins and metabolites to assess and engineer microbial isopentenol production. In: Biotechnology and Bioengineering. 2014 ; Vol. 111, No. 8. pp. 1648-1658.

Bibtex

@article{974a1cab58624ae4ad9ba43d401e0aef,
title = "Correlation analysis of targeted proteins and metabolites to assess and engineer microbial isopentenol production",
abstract = "The ability to rapidly assess and optimize heterologous pathway function is critical for effective metabolic engineering. Here, we develop a systematic approach to pathway analysis based on correlations between targeted proteins and metabolites and apply it to the microbial production of isopentenol, a promising biofuel. Starting with a seven-gene pathway, we performed a correlation analysis to reduce pathway complexity and identified two pathway proteins as the primary determinants of efficient isopentenol production. Aided by the targeted quantification of relevant pathway intermediates, we constructed and subsequently validated a conceptual model of isopentenol pathway function. Informed by our analysis, we assembled a strain which produced isopentenol at a titer 1.5 g/L, or 46% of theoretical yield. Our engineering approach allowed us to accurately identify bottlenecks and determine appropriate pathway balance. Paired with high-throughput cloning techniques and analytics, this strategy should prove useful for the analysis and optimization of increasingly complex heterologous pathways.",
keywords = "Acetates/metabolism, Biofuels/microbiology, Biosynthetic Pathways, Escherichia coli/genetics, Escherichia coli Proteins/genetics, Glucose/metabolism, Industrial Microbiology/methods, Metabolic Engineering/methods, Models, Biological, Pentanols/metabolism, Proteomics/methods",
author = "George, {Kevin W} and Amy Chen and Aakriti Jain and Batth, {Tanveer S} and Baidoo, {Edward E K} and George Wang and Adams, {Paul D} and Petzold, {Christopher J} and Keasling, {Jay D} and Lee, {Taek Soon}",
note = "{\textcopyright} 2014 Wiley Periodicals, Inc.",
year = "2014",
doi = "10.1002/bit.25226",
language = "English",
volume = "111",
pages = "1648--1658",
journal = "Biotechnology and Bioengineering",
issn = "0006-3592",
publisher = "JohnWiley & Sons, Inc.",
number = "8",

}

RIS

TY - JOUR

T1 - Correlation analysis of targeted proteins and metabolites to assess and engineer microbial isopentenol production

AU - George, Kevin W

AU - Chen, Amy

AU - Jain, Aakriti

AU - Batth, Tanveer S

AU - Baidoo, Edward E K

AU - Wang, George

AU - Adams, Paul D

AU - Petzold, Christopher J

AU - Keasling, Jay D

AU - Lee, Taek Soon

N1 - © 2014 Wiley Periodicals, Inc.

PY - 2014

Y1 - 2014

N2 - The ability to rapidly assess and optimize heterologous pathway function is critical for effective metabolic engineering. Here, we develop a systematic approach to pathway analysis based on correlations between targeted proteins and metabolites and apply it to the microbial production of isopentenol, a promising biofuel. Starting with a seven-gene pathway, we performed a correlation analysis to reduce pathway complexity and identified two pathway proteins as the primary determinants of efficient isopentenol production. Aided by the targeted quantification of relevant pathway intermediates, we constructed and subsequently validated a conceptual model of isopentenol pathway function. Informed by our analysis, we assembled a strain which produced isopentenol at a titer 1.5 g/L, or 46% of theoretical yield. Our engineering approach allowed us to accurately identify bottlenecks and determine appropriate pathway balance. Paired with high-throughput cloning techniques and analytics, this strategy should prove useful for the analysis and optimization of increasingly complex heterologous pathways.

AB - The ability to rapidly assess and optimize heterologous pathway function is critical for effective metabolic engineering. Here, we develop a systematic approach to pathway analysis based on correlations between targeted proteins and metabolites and apply it to the microbial production of isopentenol, a promising biofuel. Starting with a seven-gene pathway, we performed a correlation analysis to reduce pathway complexity and identified two pathway proteins as the primary determinants of efficient isopentenol production. Aided by the targeted quantification of relevant pathway intermediates, we constructed and subsequently validated a conceptual model of isopentenol pathway function. Informed by our analysis, we assembled a strain which produced isopentenol at a titer 1.5 g/L, or 46% of theoretical yield. Our engineering approach allowed us to accurately identify bottlenecks and determine appropriate pathway balance. Paired with high-throughput cloning techniques and analytics, this strategy should prove useful for the analysis and optimization of increasingly complex heterologous pathways.

KW - Acetates/metabolism

KW - Biofuels/microbiology

KW - Biosynthetic Pathways

KW - Escherichia coli/genetics

KW - Escherichia coli Proteins/genetics

KW - Glucose/metabolism

KW - Industrial Microbiology/methods

KW - Metabolic Engineering/methods

KW - Models, Biological

KW - Pentanols/metabolism

KW - Proteomics/methods

U2 - 10.1002/bit.25226

DO - 10.1002/bit.25226

M3 - Journal article

C2 - 24615242

VL - 111

SP - 1648

EP - 1658

JO - Biotechnology and Bioengineering

JF - Biotechnology and Bioengineering

SN - 0006-3592

IS - 8

ER -

ID: 204046836