Metabolic engineering of Corynebacterium glutamicum for the production of glutaric acid, a C5 dicarboxylic acid platform chemical

Hee Taek Kim; Tae Uk Khang; Kei Anne Baritugo; Sung Min Hyun; Kyoung Hee Kang; Sol Hee Jung; Bong Keun Song; Kyungmoon Park; Min Kyu Oh; Gi Bae Kim; Hyun Uk Kim; Sang Yup Lee; Si Jae Park; Jeong Chan Joo

doi:10.1016/j.ymben.2018.08.007

Metabolic engineering of Corynebacterium glutamicum for the production of glutaric acid, a C5 dicarboxylic acid platform chemical

Hee Taek Kim, Tae Uk Khang, Kei Anne Baritugo, Sung Min Hyun, Kyoung Hee Kang, Sol Hee Jung, Bong Keun Song, Kyungmoon Park, Min Kyu Oh, Gi Bae Kim, Hyun Uk Kim, Sang Yup Lee, Si Jae Park, Jeong Chan Joo

Department of Chemical Engineering & Materials Science

Research output: Contribution to journal › Article › peer-review

51 Scopus citations

Abstract

Corynebacterium glutamicum was metabolically engineered for the production of glutaric acid, a C5 dicarboxylic acid that can be used as platform building block chemical for nylons and plasticizers. C. glutamicum gabT and gabD genes and Pseudomonas putida davT and davD genes encoding 5-aminovalerate transaminase and glutarate semialdehyde dehydrogenase, respectively, were examined in C. glutamicum for the construction of a glutaric acid biosynthesis pathway along with P. putida davB and davA genes encoding lysine 2-monooxygenase and delta-aminovaleramidase, respectively. The glutaric acid biosynthesis pathway constructed in recombinant C. glutamicum was engineered by examining strong synthetic promoters P_H30 and P_H36, C. glutamicum codon-optimized davTDBA genes, and modification of davB gene with an N-terminal His₆-tag to improve the production of glutaric acid. It was found that use of N-terminal His₆-tagged DavB was most suitable for the production of glutaric acid from glucose. Fed-batch fermentation using the final engineered C. glutamicum H30_GA_His strain, expressing davTDA genes along with davB fused with His₆-tag at N-terminus could produce 24.5 g/L of glutaric acid with low accumulation of L-lysine (1.7 g/L), wherein 5-AVA accumulation was not observed during fermentation.

Original language	English
Pages (from-to)	99-109
Number of pages	11
Journal	Metabolic Engineering
Volume	51
DOIs	https://doi.org/10.1016/j.ymben.2018.08.007
State	Published - Jan 2019

Bibliographical note

Funding Information:
This work was supported by the Mid-career Researcher Program through the National Research Foundation (NRF) of Korea funded by the Ministry of Science and ICT (MSIT) ( NRF-2016R1A2B4008707 ), the Technology Development Program to Solve Climate Changes on Systems Metabolic Engineering for Biorefineries from MSIT through the NRF of Korea ( NRF-2015M1A2A2035810 ), the Bio & Medical Technology Development Program MSIT through the NRF of Korea ( NRF-2018M3A9H3020459 ) and the Lignin Biorefinery from MSIT through the NRF of Korea ( NRF-2017M1A2A2087634 ).

Publisher Copyright:
© 2018 International Metabolic Engineering Society

Keywords

Codon optimization
Corynebacterium glutamicum
davTDBA
Fed-batch fermentation
Glutaric acid
His-tag
L‐Lysine

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10.1016/j.ymben.2018.08.007

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Kim, H. T., Khang, T. U., Baritugo, K. A., Hyun, S. M., Kang, K. H., Jung, S. H., Song, B. K., Park, K., Oh, M. K., Kim, G. B., Kim, H. U., Lee, S. Y., Park, S. J., & Joo, J. C. (2019). Metabolic engineering of Corynebacterium glutamicum for the production of glutaric acid, a C5 dicarboxylic acid platform chemical. Metabolic Engineering, 51, 99-109. https://doi.org/10.1016/j.ymben.2018.08.007

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title = "Metabolic engineering of Corynebacterium glutamicum for the production of glutaric acid, a C5 dicarboxylic acid platform chemical",

abstract = "Corynebacterium glutamicum was metabolically engineered for the production of glutaric acid, a C5 dicarboxylic acid that can be used as platform building block chemical for nylons and plasticizers. C. glutamicum gabT and gabD genes and Pseudomonas putida davT and davD genes encoding 5-aminovalerate transaminase and glutarate semialdehyde dehydrogenase, respectively, were examined in C. glutamicum for the construction of a glutaric acid biosynthesis pathway along with P. putida davB and davA genes encoding lysine 2-monooxygenase and delta-aminovaleramidase, respectively. The glutaric acid biosynthesis pathway constructed in recombinant C. glutamicum was engineered by examining strong synthetic promoters PH30 and PH36, C. glutamicum codon-optimized davTDBA genes, and modification of davB gene with an N-terminal His6-tag to improve the production of glutaric acid. It was found that use of N-terminal His6-tagged DavB was most suitable for the production of glutaric acid from glucose. Fed-batch fermentation using the final engineered C. glutamicum H30_GAHis strain, expressing davTDA genes along with davB fused with His6-tag at N-terminus could produce 24.5 g/L of glutaric acid with low accumulation of L-lysine (1.7 g/L), wherein 5-AVA accumulation was not observed during fermentation.",

keywords = "Codon optimization, Corynebacterium glutamicum, davTDBA, Fed-batch fermentation, Glutaric acid, His-tag, L‐Lysine",

author = "Kim, {Hee Taek} and Khang, {Tae Uk} and Baritugo, {Kei Anne} and Hyun, {Sung Min} and Kang, {Kyoung Hee} and Jung, {Sol Hee} and Song, {Bong Keun} and Kyungmoon Park and Oh, {Min Kyu} and Kim, {Gi Bae} and Kim, {Hyun Uk} and Lee, {Sang Yup} and Park, {Si Jae} and Joo, {Jeong Chan}",

note = "Funding Information: This work was supported by the Mid-career Researcher Program through the National Research Foundation (NRF) of Korea funded by the Ministry of Science and ICT (MSIT) ( NRF-2016R1A2B4008707 ), the Technology Development Program to Solve Climate Changes on Systems Metabolic Engineering for Biorefineries from MSIT through the NRF of Korea ( NRF-2015M1A2A2035810 ), the Bio & Medical Technology Development Program MSIT through the NRF of Korea ( NRF-2018M3A9H3020459 ) and the Lignin Biorefinery from MSIT through the NRF of Korea ( NRF-2017M1A2A2087634 ). Publisher Copyright: {\textcopyright} 2018 International Metabolic Engineering Society",

year = "2019",

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doi = "10.1016/j.ymben.2018.08.007",

language = "English",

volume = "51",

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AU - Kim, Hee Taek

AU - Khang, Tae Uk

AU - Baritugo, Kei Anne

AU - Hyun, Sung Min

AU - Kang, Kyoung Hee

AU - Jung, Sol Hee

AU - Song, Bong Keun

AU - Park, Kyungmoon

AU - Oh, Min Kyu

AU - Kim, Gi Bae

AU - Kim, Hyun Uk

AU - Lee, Sang Yup

AU - Park, Si Jae

AU - Joo, Jeong Chan

N1 - Funding Information: This work was supported by the Mid-career Researcher Program through the National Research Foundation (NRF) of Korea funded by the Ministry of Science and ICT (MSIT) ( NRF-2016R1A2B4008707 ), the Technology Development Program to Solve Climate Changes on Systems Metabolic Engineering for Biorefineries from MSIT through the NRF of Korea ( NRF-2015M1A2A2035810 ), the Bio & Medical Technology Development Program MSIT through the NRF of Korea ( NRF-2018M3A9H3020459 ) and the Lignin Biorefinery from MSIT through the NRF of Korea ( NRF-2017M1A2A2087634 ). Publisher Copyright: © 2018 International Metabolic Engineering Society

PY - 2019/1

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N2 - Corynebacterium glutamicum was metabolically engineered for the production of glutaric acid, a C5 dicarboxylic acid that can be used as platform building block chemical for nylons and plasticizers. C. glutamicum gabT and gabD genes and Pseudomonas putida davT and davD genes encoding 5-aminovalerate transaminase and glutarate semialdehyde dehydrogenase, respectively, were examined in C. glutamicum for the construction of a glutaric acid biosynthesis pathway along with P. putida davB and davA genes encoding lysine 2-monooxygenase and delta-aminovaleramidase, respectively. The glutaric acid biosynthesis pathway constructed in recombinant C. glutamicum was engineered by examining strong synthetic promoters PH30 and PH36, C. glutamicum codon-optimized davTDBA genes, and modification of davB gene with an N-terminal His6-tag to improve the production of glutaric acid. It was found that use of N-terminal His6-tagged DavB was most suitable for the production of glutaric acid from glucose. Fed-batch fermentation using the final engineered C. glutamicum H30_GAHis strain, expressing davTDA genes along with davB fused with His6-tag at N-terminus could produce 24.5 g/L of glutaric acid with low accumulation of L-lysine (1.7 g/L), wherein 5-AVA accumulation was not observed during fermentation.

AB - Corynebacterium glutamicum was metabolically engineered for the production of glutaric acid, a C5 dicarboxylic acid that can be used as platform building block chemical for nylons and plasticizers. C. glutamicum gabT and gabD genes and Pseudomonas putida davT and davD genes encoding 5-aminovalerate transaminase and glutarate semialdehyde dehydrogenase, respectively, were examined in C. glutamicum for the construction of a glutaric acid biosynthesis pathway along with P. putida davB and davA genes encoding lysine 2-monooxygenase and delta-aminovaleramidase, respectively. The glutaric acid biosynthesis pathway constructed in recombinant C. glutamicum was engineered by examining strong synthetic promoters PH30 and PH36, C. glutamicum codon-optimized davTDBA genes, and modification of davB gene with an N-terminal His6-tag to improve the production of glutaric acid. It was found that use of N-terminal His6-tagged DavB was most suitable for the production of glutaric acid from glucose. Fed-batch fermentation using the final engineered C. glutamicum H30_GAHis strain, expressing davTDA genes along with davB fused with His6-tag at N-terminus could produce 24.5 g/L of glutaric acid with low accumulation of L-lysine (1.7 g/L), wherein 5-AVA accumulation was not observed during fermentation.

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KW - Corynebacterium glutamicum

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KW - Fed-batch fermentation

KW - Glutaric acid

KW - His-tag

KW - L‐Lysine

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Metabolic engineering of Corynebacterium glutamicum for the production of glutaric acid, a C5 dicarboxylic acid platform chemical

Abstract

Bibliographical note

Keywords

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