Continuous-Flow Microreactor-Enhanced Clean NAD+Regeneration for Biosynthesis of 7-Oxo-lithocholic Acid

Hai Peng Li; Zhi Neng You; Yuan Yang Liu; Gao Wei Zheng; Heng Gong; Yiming Mo; Ning Zhu; Yun Peng Bai; Jian He Xu

doi:10.1021/acssuschemeng.1c06730

Continuous-Flow Microreactor-Enhanced Clean NAD⁺Regeneration for Biosynthesis of 7-Oxo-lithocholic Acid

Hai Peng Li, Zhi Neng You, Yuan Yang Liu, Gao Wei Zheng, Heng Gong, Yiming Mo, Ning Zhu, Yun Peng Bai, Jian He Xu

COLLEGE OF BIOTECHNOLOGY AND PHARMACEUTICAL ENGINEERING

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

19 Scopus citations

Abstract

Water-forming NAD(P)H oxidases (NOXs) constitute a clean NAD(P)+ regeneration strategy for NAD(P)+-dependent biotransformations to produce high value-added chemicals because they only consume oxygen and generate water. However, the application of NOXs is still challenging because of limited oxygen transfer in batch reactions. Here, we report an efficient continuous-flow microreactor (CFMR) to improve the oxygen transfer and reaction performance in NAD+-dependent chenodeoxycholic acid oxidation catalyzed by 7α-hydroxysteroid dehydrogenase (7α-HSDH) for the production of 7-oxo-lithocholic acid, a key precursor of ursodeoxycholic acid. The recycling efficiency of NAD+ by NOX from Streptococcus mutans (SmNOX) was significantly improved in this CFMR. Compared with a conventional batch stirred tank reactor, the space-time yield of production of 7-oxo-lithocholic acid was increased by 96-fold. Furthermore, the total turnover number of NAD+ was improved 10-fold, and the enzyme consumption number was decreased 7-fold. Combining the NOX/O2 system with this microreactor technology provides a general platform that enables various NAD(P)+-dependent biotransformations in a green and sustainable manner, which will be helpful in the design of ecofriendly bioprocesses for production of functional chemicals on a large scale.

Original language	English
Pages (from-to)	456-463
Number of pages	8
Journal	ACS Sustainable Chemistry and Engineering
Volume	10
Issue number	1
DOIs	https://doi.org/10.1021/acssuschemeng.1c06730
State	Published - 10 Jan 2022

Keywords

Cofactor regeneration
Continuous-flow microreactor
Enzyme consumption number
NAD(P)H oxidases
Oxygen transfer
Space-time yield
Total turnover number

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1021/acssuschemeng.1c06730

Cite this

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title = "Continuous-Flow Microreactor-Enhanced Clean NAD+Regeneration for Biosynthesis of 7-Oxo-lithocholic Acid",

abstract = "Water-forming NAD(P)H oxidases (NOXs) constitute a clean NAD(P)+ regeneration strategy for NAD(P)+-dependent biotransformations to produce high value-added chemicals because they only consume oxygen and generate water. However, the application of NOXs is still challenging because of limited oxygen transfer in batch reactions. Here, we report an efficient continuous-flow microreactor (CFMR) to improve the oxygen transfer and reaction performance in NAD+-dependent chenodeoxycholic acid oxidation catalyzed by 7α-hydroxysteroid dehydrogenase (7α-HSDH) for the production of 7-oxo-lithocholic acid, a key precursor of ursodeoxycholic acid. The recycling efficiency of NAD+ by NOX from Streptococcus mutans (SmNOX) was significantly improved in this CFMR. Compared with a conventional batch stirred tank reactor, the space-time yield of production of 7-oxo-lithocholic acid was increased by 96-fold. Furthermore, the total turnover number of NAD+ was improved 10-fold, and the enzyme consumption number was decreased 7-fold. Combining the NOX/O2 system with this microreactor technology provides a general platform that enables various NAD(P)+-dependent biotransformations in a green and sustainable manner, which will be helpful in the design of ecofriendly bioprocesses for production of functional chemicals on a large scale.",

keywords = "Cofactor regeneration, Continuous-flow microreactor, Enzyme consumption number, NAD(P)H oxidases, Oxygen transfer, Space-time yield, Total turnover number",

author = "Li, {Hai Peng} and You, {Zhi Neng} and Liu, {Yuan Yang} and Zheng, {Gao Wei} and Heng Gong and Yiming Mo and Ning Zhu and Bai, {Yun Peng} and Xu, {Jian He}",

note = "Publisher Copyright: {\textcopyright} 2021 American Chemical Society.",

year = "2022",

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T1 - Continuous-Flow Microreactor-Enhanced Clean NAD+Regeneration for Biosynthesis of 7-Oxo-lithocholic Acid

AU - Li, Hai Peng

AU - You, Zhi Neng

AU - Liu, Yuan Yang

AU - Zheng, Gao Wei

AU - Gong, Heng

AU - Mo, Yiming

AU - Zhu, Ning

AU - Bai, Yun Peng

AU - Xu, Jian He

PY - 2022/1/10

Y1 - 2022/1/10

N2 - Water-forming NAD(P)H oxidases (NOXs) constitute a clean NAD(P)+ regeneration strategy for NAD(P)+-dependent biotransformations to produce high value-added chemicals because they only consume oxygen and generate water. However, the application of NOXs is still challenging because of limited oxygen transfer in batch reactions. Here, we report an efficient continuous-flow microreactor (CFMR) to improve the oxygen transfer and reaction performance in NAD+-dependent chenodeoxycholic acid oxidation catalyzed by 7α-hydroxysteroid dehydrogenase (7α-HSDH) for the production of 7-oxo-lithocholic acid, a key precursor of ursodeoxycholic acid. The recycling efficiency of NAD+ by NOX from Streptococcus mutans (SmNOX) was significantly improved in this CFMR. Compared with a conventional batch stirred tank reactor, the space-time yield of production of 7-oxo-lithocholic acid was increased by 96-fold. Furthermore, the total turnover number of NAD+ was improved 10-fold, and the enzyme consumption number was decreased 7-fold. Combining the NOX/O2 system with this microreactor technology provides a general platform that enables various NAD(P)+-dependent biotransformations in a green and sustainable manner, which will be helpful in the design of ecofriendly bioprocesses for production of functional chemicals on a large scale.

AB - Water-forming NAD(P)H oxidases (NOXs) constitute a clean NAD(P)+ regeneration strategy for NAD(P)+-dependent biotransformations to produce high value-added chemicals because they only consume oxygen and generate water. However, the application of NOXs is still challenging because of limited oxygen transfer in batch reactions. Here, we report an efficient continuous-flow microreactor (CFMR) to improve the oxygen transfer and reaction performance in NAD+-dependent chenodeoxycholic acid oxidation catalyzed by 7α-hydroxysteroid dehydrogenase (7α-HSDH) for the production of 7-oxo-lithocholic acid, a key precursor of ursodeoxycholic acid. The recycling efficiency of NAD+ by NOX from Streptococcus mutans (SmNOX) was significantly improved in this CFMR. Compared with a conventional batch stirred tank reactor, the space-time yield of production of 7-oxo-lithocholic acid was increased by 96-fold. Furthermore, the total turnover number of NAD+ was improved 10-fold, and the enzyme consumption number was decreased 7-fold. Combining the NOX/O2 system with this microreactor technology provides a general platform that enables various NAD(P)+-dependent biotransformations in a green and sustainable manner, which will be helpful in the design of ecofriendly bioprocesses for production of functional chemicals on a large scale.

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