微生物合成二元醇研究进展

竺方欢; 岑雪聪; 陈振

doi:10.12211/2096-8280.2024-014

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微生物合成二元醇研究进展

特约评述 | 更新时间：2025-04-11

- 微生物合成二元醇研究进展
- Research progress of diols production by microbes
- 合成生物学 2024年5卷第6期页码：1367-1385
- 作者机构：
  
  1.清华大学化学工程系，工业生物催化教育部重点实验室，北京 100084
  2.清华大学合成与系统生物学中心，北京 100084
- 作者简介：
  
  [ "竺方欢（1996—），女，博士研究生。研究方向为二元醇的绿色生物制造。E-mail：zfh21@mails.tsinghua.edu.cn" ]
  [ "岑雪聪（1996—），女，博士研究生。研究方向为二元醇的绿色生物制造。 E-mail：cxc18@mails.tsinghua.edu.cn" ]
  [ "陈振（1983—），男，副教授，博士生导师。研究方向为材料、化学品及生物医药的绿色生物制造。E-mail：zhenchen2013@tsinghua.edu.cn" ]
- 基金信息：
  
  国家重点研发计划(2021YFC2100900);国家自然科学基金(22078172;21938004)
- DOI：10.12211/2096-8280.2024-014
  中图分类号： Q812
- 收稿：2024-02-04，
  
  修回：2024-05-08，
  
  纸质出版：2024-12-31
- 稿件说明：
移动端阅览
竺方欢，岑雪聪，陈振. 微生物合成二元醇研究进展［J］. 合成生物学， 2024， 5（6）： 1367-1385

ZHU Fanghuan， CEN Xuecong， CHEN Zhen. Research progress of diols production by microbes［J］. Synthetic Biology Journal， 2024， 5（6）： 1367-1385
竺方欢，岑雪聪，陈振. 微生物合成二元醇研究进展［J］. 合成生物学， 2024， 5（6）： 1367-1385 DOI： 10.12211/2096-8280.2024-014.

ZHU Fanghuan， CEN Xuecong， CHEN Zhen. Research progress of diols production by microbes［J］. Synthetic Biology Journal， 2024， 5（6）： 1367-1385 DOI： 10.12211/2096-8280.2024-014.

摘要

二元醇是一类重要的大宗化学品，在高分子材料、化妆品、燃料、食品和制药行业有着广泛应用。开发可利用生物质及碳一原料等可再生原料生产二元醇的生物合成路线对于降低化石资源依赖、减少二氧化碳的排放具有重要意义，近年来受到了国内外广泛关注。虽然通过生物法生产1，3-丙二醇、1，3-丁二醇和1，4-丁二醇已实现商业化，但大多数其他二元醇的高效生物合成仍面临挑战，主要原因包括缺乏有效的天然生物合成途径、基因工程菌的产率低等。本综述全面探讨了微生物合成二元醇的最新研究进展，特别是在开发新代谢途径和代谢工程策略方面，以实现C

至C

二元醇的高效生物合成。例如通过对非天然合成途径的设计和构建以实现系列非天然二元醇的生物合成，以及利用非传统的碳源（如木质纤维素等）通过特定的代谢途径和优化策略合成二元醇，为生物合成领域开辟新的道路。此外，本文还讨论了这些生物合成过程向工业应用转化的主要挑战和未来的发展前景，包括廉价和可持续原料的获取、大规模放大过程的复杂性、满足下游特定需求的后提取工艺开发等。

Abstract

Production of chemicals using renewable bioresources and green biomanufacturing processes is highly important for sustainable bioeconomy. Diols are important bulk chemicals widely used in the production of polymers

cosmetics

fuels

food

and pharmaceutical industries due to their versatile functional properties. Currently

most of diols are produced mainly from fossil resources

via

energy-cost chemical approaches. The development of biosynthetic routes for the production of diols from renewable resourc

es such as biomass and C

has garnered significant attention due to its potential in reducing the utilization of fossil resources and carbon dioxide emissions. Although biological production of 1

3-propanediol

3-butanediol and 1

4-butanediol has been commercialized

the biosynthesis of other major diols remains challenging due to the absence of efficient natural biosynthetic pathways and low efficiency of the recombinant microbes. Recent development of metabolic engineering and synthetic biology enables the production of non-natural chemicals

via

artificial metabolic pathways and novel biological parts

significantly expanding the boundary of biomanufacturing. This review comprehensively explores recent advances in the microbial synthesis of diols

emphasizing the development of new pathways and engineering strategies for the biosynthesis of C

to C

diols. Especially

we focus on the innovative approaches include constructing non-natural synthetic pathways to achieve the biosynthesis of non-natural diols

or using alternative carbon sources such as lignocellulose through specific metabolic pathways to synthesize diols. Furthermore

this review also discusses the primary challenges and future perspectives in transforming these biosynthetic processes toward industrial applications. Key challenges involve the accessibility of low-cost and sustainable raw materials

the complexities in scaling up these processes

the development of extraction techniques that cater to specific downstream requirements

and the economic assessment of these processes to ensure profitability and sustainability. These advancements are essential for the economic and environmental viability of producing diols from renewable resources

thereby facilitating the transition to more sustainable industrial practices globally.

关键词

Keywords

references

CHOI S , SONG C W , SHIN J H , et al . Biorefineries for the production of top building block chemicals and their derivatives [J ] . Metabolic Engineering , 2015 , 28 : 223 - 239 .

LIU Y F , WANG W , ZENG A P . Biosynthesizing structurally diverse diols via a general route combining oxidative and reductive formations of OH-groups [J ] . Nature Communications , 2022 , 13 ( 1 ): 1595 .

LIU Y , CEN X C , LIU D H , et al . Metabolic engineering of Escherichia coli for high-yield production of ( R )-1,3-butanediol [J ] . ACS Synthetic Biology , 2021 , 10 ( 8 ): 1946 - 1955 .

ZHANG Y , LIU D H , CHEN Z . Production of C 2 -C 4 diols from renewable bioresources: new metabolic pathways and metabolic engineering strategies [J ] . Biotechnology for Biofuels , 2017 , 10 : 299 .

CEN X C , LIU Y J , ZHU F H , et al . Metabolic engineering of Escherichia coli for high production of 1,5-pentanediol via a cadaverine-derived pathway [J ] . Metabolic Engineering , 2022 , 74 : 168 - 177 .

CEN X C , DONG Y , LIU D H , et al . New pathways and metabolic engineering strategies for microbial synthesis of diols [J ] . Current Opinion in Biotechnology , 2022 , 78 : 102845 .

VIVEK N , HAZEENA S H , ALPHY M P , et al . Recent advances in microbial biosynthesis of C 3 -C 5 diols: genetics and process engineering approaches [J ] . Bioresource Technology , 2021 , 322 : 124527 .

WU T , LIU Y M , LIU J S , et al . Metabolic engineering and regulation of diol biosynthesis from renewable biomass in Escherichia coli [J ] . Biomolecules , 2022 , 12 ( 5 ): 715 .

陈勇 , 李凤梅 , 韩荣伟 , 等 . 酵母不对称催化制备 R -1,2丙二醇 [J ] . 生物加工过程 , 2009 , 7 ( 4 ): 61 - 64 .

CHEN Y , LI F M , HAN R W , et al . Preparation of ( R )-1,2-propanediol through asymmetric reduction with bakers yeast [J ] . Chinese Journal of Bioprocess Engineering , 2009 , 7 ( 4 ): 61 - 64 .

MATSUYAMA A , YAMAMOTO H , KAWADA N , et al . Industrial production of ( R )-1,3-butanediol by new biocatalysts [J ] . Journal of Molecular Catalysis B: Enzymatic , 2001 , 11 ( 4/5/6 ): 513 - 521 .

ZHU F H , LIU D H , CHEN Z . Recent advances in biological production of 1,3-propanediol: new routes and engineering strategies [J ] . Green Chemistry , 2022 , 24 ( 4 ): 1390 - 1403 .

BURGARD A , BURK M J , OSTERHOUT R , et al . Development of a commercial scale process for production of 1,4-butanediol from sugar [J ] . Current Opinion in Biotechnology , 2016 , 42 : 118 - 125 .

SALUSJÄRVI L , HAVUKAINEN S , KOIVISTOINEN O , et al . Biotechnological production of glycolic acid and ethylene glycol: current state and perspectives [J ] . Applied Microbiology and Biotechnology , 2019 , 103 ( 6 ): 2525 - 2535 .

YUE H R , ZHAO Y J , MA X B , et al . Ethylene glycol: properties, synthesis, and applications [J ] . Chemical Society Reviews , 2012 , 41 ( 11 ): 4218 - 4244 .

CHAE T U , CHOI S Y , RYU J Y , et al . Production of ethylene glycol from xylose by metabolically engineered Escherichia coli [J ] . AIChE Journal , 2018 , 64 ( 12 ): 4193 - 4200 .

WANG Y H , XIAN M , FENG X J , et al . Biosynthesis of ethylene glycol from D-xylose in recombinant Escherichia coli [J ] . Bioengineered , 2018 , 9 ( 1 ): 233 - 241 .

PEREIRA B , LI Z J , DE MEY M , et al . Efficient utilization of pentoses for bioproduction of the renewable two-carbon compounds ethylene glycol and glycolate [J ] . Metabolic Engineering , 2016 , 34 : 80 - 87 .

URANUKUL B , WOOLSTON B M , FINK G R , et al . Biosynthesis of monoethylene glycol in Saccharomyces cerevisiae utilizing native glycolytic enzymes [J ] . Metabolic Engineering , 2019 , 51 : 20 - 31 .

ALKIM C , CAM Y , TRICHEZ D , et al . Optimization of ethylene glycol production from (D)-xylose via a synthetic pathway implemented in Escherichia coli [J ] . Microbial Cell Factories , 2015 , 14 : 127 .

PEREIRA B , ZHANG H R , DE MEY M , et al . Engineering a novel biosynthetic pathway in Escherichia coli for production of renewable ethylene glycol [J ] . Biotechnology and Bioengineering , 2016 , 113 ( 2 ): 376 - 383 .

CHEN Z , HUANG J H , WU Y , et al . Metabolic engineering of Corynebacterium glutamicum for the de novo production of ethylene glycol from glucose [J ] . Metabolic Engineering , 2016 , 33 : 12 - 18 .

SUN S Q , SHU L , LU X Y , et al . 1,2-Propanediol production from glycerol via an endogenous pathway of Klebsiella pneumoniae [J ] . Applied Microbiology and Biotechnology , 2021 , 105 ( 23 ): 9003 - 9016 .

JAIN R , SUN X X , YUAN Q P , et al . Systematically engineering Escherichia coli for enhanced production of 1,2-propanediol and 1-propanol [J ] . ACS Synthetic Biology , 2015 , 4 ( 6 ): 746 - 756 .

NIU W , KRAMER L , MUELLER J , et al . Metabolic engineering of Escherichia coli for the de novo stereospecific biosynthesis of 1,2-propanediol through lactic acid [J ] . Metabolic Engineering Communications , 2019 , 8 : e00082 .

KURIAN J V . A new polymer platform for the future—sorona ® from corn derived 1,3-prop anediol [J ] . Journal of Polymers and the Environment , 2005 , 13 ( 2 ): 159 - 167 .

LI Z H , DONG Y F , LIU Y , et al . Systems metabolic engineering of Corynebacterium glutamicum for high-level production of 1,3-propanediol from glucose and xylose [J ] . Metabolic Engineering , 2022 , 70 : 79 - 88 .

ZHANG Y , SUN Q , LIU Y , et al . Development of a plasmid stabilization system in Vibrio natriegens for the high production of 1,3-propanediol and 3-hydroxypropionate [J ] . Bioresources and Bioprocessing , 2021 , 8 ( 1 ): 125 .

ZHANG Y J , MA C W , DISCHERT W , et al . Engineering of phosphoserine aminotransferase increases the conversion of L-homoserine to 4-hydroxy-2-ketobutyrate in a glycerol-independent pathway of 1,3-propanediol production from glucose [J ] . Biotechnology Journal , 2019 , 14 ( 9 ): e1900003 .

LI Z H , WU Z Y , CEN X C , et al . Efficient production of 1,3-propanediol from diverse carbohydrates via a non-natural pathway using 3-hydroxypropionic acid as an intermediate [J ] . ACS Synthetic Biology , 2021 , 10 ( 3 ): 478 - 486 .

LI M D , ZHANG Y , LI J C , et al . Biosynthesis of 1,3-propanediol via a new pathway from glucose in Escherichia coli [J ] . ACS Synthetic Biology , 2023 , 12 ( 7 ): 2083 - 2093 .

KATAOKA N , VANGNAI A S , UEDA H , et al . Enhancement of ( R )-1,3-butanediol production by engineered Escherichia coli using a bioreactor system with strict regulation of overall oxygen transfer coefficient and pH [J ] . Bioscience, Biotechnology, and Biochemistry , 2014 , 78 ( 4 ): 695 - 700 .

WANG J , ZHANG R H , ZHANG J L , et al . Tunable hybrid carbon metabolism coordination for the carbon-efficient biosynthesis of 1,3-butanediol in Escherichia coli [J ] . Green Chemistry , 2021 , 23 ( 21 ): 8694 - 8706 .

ISLAM T , NGUYEN-VO T P , GAUR V K , et al . Metabolic engin eering of Escherichia coli for biological production of 1,3-butanediol [J ] . Bioresource Technology , 2023 , 376 : 128911 .

ISLAM T , NGUYEN-VO T P , CHO S , et al . Metabolic engineering of Escherichia coli for enhanced production of 1,3-butanediol from glucose [J ] . Bioresource Technology , 2023 , 389 : 129814 .

KIM T , FLICK R , BRUNZELLE J , et al . Novel Aldo-Keto reductases for the biocatalytic conversion of 3-hydroxybutanal to 1,3-butanediol: structural and biochemical studies [J ] . Applied and Environmental Microbiology , 2017 , 83 ( 7 ): e03172-16 .

WANG J , LI C Y , ZOU Y S , et al . Bacterial synthesis of C 3 -C 5 diols via extending amino acid catabolism [J ] . Proceedings of the National Academy of Sciences of the United States of America , 2020 , 117 ( 32 ): 19159 - 19167 .

TAI Y S , XIONG M Y , JAMBUNATHAN P , et al . Engineering nonphosphorylative metabolism to generate lignocellulose-derived products [J ] . Nature Chemical Biology , 2016 , 12 ( 4 ): 247 - 253 .

QIN N , ZHU F H , LIU Y Y , et al . Metabolic engineering of Escherichia coli for de novo production of 1,2-butanediol [J ] . ACS Synthetic Biology , 2024 , 13 ( 1 ): 351 - 357 .

LEE Y G , SEO J H . Production of 2,3-butanediol from glucose and cassava hydrolysates by metabolically engineered industrial polyploid Saccharomyces cerevisiae [J ] . Biotechnology for Biofuels , 2019 , 12 : 204 .

KOU M Y , CUI Z Z , FU J , et al . Metabolic engineering of Corynebacterium glutamicum for efficient production of optically pure (2 R ,3 R )-2,3-butanediol [J ] . Microbial Cell Factories , 2022 , 21 ( 1 ): 150 .

CEN X C , LIU Y , CHEN B , et al . Metabolic engineering of Escherichia coli for de novo production of 1,5-pentanediol from glucose [J ] . ACS Synthetic Biology , 2021 , 10 ( 1 ): 192 - 203 .

TAO Y M , BU C Y , ZOU L H , et al . A comprehensive review on microbial production of 1,2-propanediol: micro-organisms, metabolic pathways, and metabolic engineering [J ] . Biotechnology for Biofuels , 2021 , 14 ( 1 ): 216 .

MARINAS A , BRUIJNINCX P , FTOUNI J , et al . Sustainability metrics for a fossil- and renewable-based route for 1,2-propanediol production: a comparison [J ] . Catalysis Today , 2015 , 239 : 31 - 37 .

INGVADOTTIR E M , SCULLY S M , ORLYGSSON J . Production of ( S )-1,2-propanediol from L-rhamnose using the moderately thermophilic Clostridium strain AK1 [J ] . Anaerobe , 2018 , 54 : 26 - 30 .

BADÍA J , ROS J , AGUILAR J . Fermentation mechanism of fucose and rhamnose in Salmonella typhimurium and Klebsiella pneumoniae [J ] . Journal of Bacteriology , 1985 , 161 ( 1 ): 435 - 437 .

JUN S A , MOON C , KANG C H , et al . Microbial fed-batch production of 1,3-propanediol using raw glycerol with suspended and immobilized Klebsiella pneumoniae [J ] . Applied Biochemistry and Biotechnology , 2010 , 161 ( 1-8 ): 491 - 501 .

LIU H J , XU Y Z , ZHENG Z M , et al . 1, 3-Propanediol and its copolymers: research, development and industrialization [J ] . Biotechnology Journal , 2010 , 5 ( 11 ): 1137 - 1148 .

YANG M M , YUN J H , ZHANG H H , et al . Genetically engineered strains: application and advances for 1,3-propanediol production from glycerol [J ] . Food Technology and Biotechnology , 2018 , 56 ( 1 ): 3 - 15 .

OH B R , LEE S M , HEO S Y , et al . Efficient production of 1,3-propanediol from crude glycerol by repeated fed-batch fermentation strategy of a lactate and 2,3-butanediol deficient mutant of Klebsiella pneumoniae [J ] . Microbial Cell Factories , 2018 , 17 ( 1 ): 92 .

ZHOU S , HUANG Y H , MAO X L , et al . Impact of acetolactate synthase inactivation on 1,3-propanediol fermentation by Klebsiella pneumoniae [J ] . PLoS One , 2019 , 14 ( 4 ): e0200978 .

CHEN Z , GENG F , ZENG A P . Protein design and engineering of a de novo pathway for microbial production of 1,3-propanediol from glucose [J ] . Biotechnology Journal , 2015 , 10 ( 2 ): 284 - 289 .

ZHONG W Q , ZHANG Y , WU W J , et al . Metabolic engineering of a homoserine-derived non-natural pathway for the de novo production of 1,3-propanediol from glucose [J ] . ACS Synthetic Biology , 2019 , 8 ( 3 ): 587 - 595 .

WALTHER T , TOPHAM C M , IRAGUE R , et al . Construction of a synthetic metabolic pathway for biosynthesis of the non-natural methionine precursor 2,4-dihydroxybutyric acid [J ] . Nature Communications , 2017 , 8 : 15828 .

FRAZÃO C J R , TRICHEZ D , SERRANO-BATAILLE H , et al . Construction of a synthetic pathway for the production of 1,3-propanediol from glucose [J ] . Scientific Reports , 2019 , 9 ( 1 ): 11576 .

ZHANG C J , SHARMA S , MA C W , et al . Strain evolution and novel downstream processing with integrated catalysis enable highly efficient coproduction of 1,3-propanediol and organic acid esters from crude glycerol [J ] . Biotechnology and Bioengineering , 2022 , 119 ( 6 ): 1450 - 1466 .

MENG H , WANG C , YUAN Q P , et al . An aldolase-based new pathway for bioconversion of formaldehyde and ethanol into 1,3-propanediol in Escherichia coli [J ] . ACS Synthetic Biology , 2021 , 10 ( 4 ): 799 - 809 .

TROTTER C L , BABU G S , WALLACE S . Engineering biology for sustainable 1,4-butanediol synthesis [J ] . Trends in Biotechnology , 2023 , 41 ( 3 ): 286 - 288 .

ZHU Y , YANG J M , MEI F , et al . Bio-based 1,4-butanediol and tetrahydrofuran synthesis: perspective [J ] . Green Chemistry , 2022 , 24 ( 17 ): 6450 - 6466 .

YIM H , HASELBECK R , NIU W , et al . Metabolic engineering of Escherichia coli for direct production of 1,4-butanediol [J ] . Nature Chemical Biology , 2011 , 7 ( 7 ): 445 - 452 .

BARTON N R , BURGARD A P , BURK M J , et al . An integrated biotechnology platform for developing sustainable chemical processes [J ] . Journal of Industrial Microbiology & Biotechnology , 2015 , 42 ( 3 ): 349 - 360 .

LIU H W , LU T . Autonomous production of 1, 4-butanediol via a de novo biosynthesis pathway in engineered Escherichia coli [J ] . Metabolic Engineering , 2015 , 29 : 135 - 141 .

WANG J , JAIN R , SHEN X L , et al . Rational engineering of diol dehydratase enables 1,4-butanediol biosynthesis from xylose [J ] . Metabolic Engineering , 2017 , 40 : 148 - 156 .

LIU X , FABOS V , TAYLOR S , et al . One-step production of 1,3-butadiene from 2,3-butanediol dehydration [J ] . Chemistry , 2016 , 22 ( 35 ): 12290 - 12294 .

BAEK H S , WOO B Y , YOO S J , et al . Composition containing meso-2 , 3 -butane diol: US 10525017 [P/OL ] . 2020-01-07 [ 2024-01-01 ] . https://ppubs.uspto.gov/dirsearch-public/print/downloadPdf/10525017 https://ppubs.uspto.gov/dirsearch-public/print/downloadPdf/10525017 .

OTAGIRI M , UI S , TAKUSAGAWA Y , et al . Structural basis for chiral substrate recognition by two 2,3-butanediol dehydrogenases [J ] . FEBS Letters , 2010 , 584 ( 1 ): 219 - 223 .

YU B , SUN J B , BOMMAREDDY R R , et al . Novel (2 R ,3 R )-2,3-butanediol dehydrogenase from potential industrial strain Paenibacillus polymyxa ATCC 12321 [J ] . Applied and Environmental Microbiology , 2011 , 77 ( 12 ): 4230 - 4233 .

LEE J W , LEE Y G , JIN Y S , et al . Metabolic engineering of non-pathogenic microorganisms for 2,3-butanediol production [J ] . Applied Microbiology and Biotechnology , 2021 , 105 ( 14/15 ): 5751 - 5767 .

MIZOBATA A , MITSUI R , YAMADA R , et al . Improvement of 2,3-butanediol tolerance in Saccharomyces cerevisiae by using a novel mutagenesis strategy [J ] . Journal of Bioscience and Bioengineering , 2021 , 131 ( 3 ): 283 - 289 .

NOVAK K , KUTSCHA R , PFLÜGL S . Microbial upgrading of acetate into 2,3-butanediol and acetoin by E . coli W [J ] . Biotechnology for Biofuels , 2020 , 13 : 177 .

REHMAN S , LENG L , ZHUANG H C , et al . Genomic insights to facilitate the construction of a high-xylose-utilization Enterococcus faecalis OPS2 for 2,3-BDO production [J ] . Chemical Engineering Journal , 2022 , 448 : 137617 .

LIN H , XU J Y , SUN W L , et al . Efficient 1-hydroxy-2-butanone production from 1,2-butanediol by whole cells of engineered E . coli [J ] . Catalysts , 2021 , 11 ( 10 ): 1184 .

LU H Y , DIAZ D J , CZARNECKI N J , et al . Machine learning-aided engineering of hydrolases for PET depolymerization [J ] . Nature , 2022 , 604 ( 7907 ): 662 - 667 .

JIANG S , WANG R R , WANG D H , et al . Metabolic reprogramming and biosensor-assisted mutagenesis screening for high-level production of L-arginine in Escherichia coli [J ] . Metabolic Engineering , 2023 , 76 : 146 - 157 .

LIN J L , WAGNER J M , ALPER H S . Enabling tools for high-throughput detection of metabolites: metabolic engineering and directed evolution applications [J ] . Biotechnology Advances , 2017 , 35 ( 8 ): 950 - 970 .

CHAE T U , CHOI S Y , KIM J W , et al . Recent advances in systems metabolic engineering tools and strategies [J ] . Current Opinion in Biotechnology , 2017 , 47 : 67 - 82 .

ZHANG Y W , YANG J W , YANG S Q , et al . Programming cells by multicopy chromosomal integration using CRISPR-associated transposases [J ] . The CRISPR Journal , 2021 , 4 ( 3 ): 350 - 359 .

DONG Y F , ZHANG Y , LIU D H , et al . Strain and process engineering toward continuous industrial fermentation [J ] . Frontiers of Chemical Science and Engineering , 2023 , 17 ( 10 ): 1336 - 1353 .

JIANG L L , LIU H F , MU Y , et al . High tolerance to glycerol and high production of 1,3-propanediol in batch fermentations by microbial consortium from marine sludge [J ] . Engineering in Life Sciences , 2017 , 17 ( 6 ): 635 - 644 .

LEE S Y , KIM H U , CHAE T U , et al . A comprehensive metabolic map for production of bio-based chemicals [J ] . Nature Catalysis , 2019 , 2 : 18 - 33 .

UTESCH T , SABRA W , PRESCHER C , et al . Enhanced electron transfer of different mediators for strictly opposite shifting of metabolism in Clostridium pasteurianum grown on glycerol in a new electrochemical bioreactor [J ] . Biotechnology and Bioengineering , 2019 , 116 ( 7 ): 1627 - 1643 .

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