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Title: A modified serine cycle in Escherichia coli coverts methanol and CO 2 to two-carbon compounds

Abstract

Microbial utilization of renewable one-carbon compounds, such as methane, methanol, formic acid, and CO 2, has emerged as a potential approach to increase the range of carbon sources for bioproduction and address climate change issues. Here, we modify the natural serine cycle present in methylotrophs and build an adapted pathway for Escherichia coli, which allows microorganism to condense methanol (or formate) together with bicarbonate to produce various products. We introduce the modified cycle into E. coli and demonstrate its capability for one-carbon assimilation through growth complementation and isotope labeling experiments. We also demonstrate conversion of methanol to ethanol by utilizing the modified serine cycle in an engineered E. coli strain, achieving a reaction yet to be accomplished by a one-pot chemical process. This research provides a platform to utilize various renewable one-carbon compounds as carbon sources for biosynthesis through a modified serine cycle in E. coli.

Authors:
 [1]; ORCiD logo [2]
  1. Univ. of California, Los Angeles, CA (United States)
  2. Academia Sinica, Taipei (Taiwan)
Publication Date:
Research Org.:
Univ. of California, Los Angeles, CA (United States)
Sponsoring Org.:
USDOE Advanced Research Projects Agency - Energy (ARPA-E)
OSTI Identifier:
1513266
Grant/Contract Number:  
AR0000201
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
Nature Communications
Additional Journal Information:
Journal Volume: 9; Journal Issue: 1; Journal ID: ISSN 2041-1723
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
English

Citation Formats

Yu, Hong, and Liao, James C. A modified serine cycle in Escherichia coli coverts methanol and CO2 to two-carbon compounds. United States: N. p., 2018. Web. doi:10.1038/s41467-018-06496-4.
Yu, Hong, & Liao, James C. A modified serine cycle in Escherichia coli coverts methanol and CO2 to two-carbon compounds. United States. doi:10.1038/s41467-018-06496-4.
Yu, Hong, and Liao, James C. Fri . "A modified serine cycle in Escherichia coli coverts methanol and CO2 to two-carbon compounds". United States. doi:10.1038/s41467-018-06496-4. https://www.osti.gov/servlets/purl/1513266.
@article{osti_1513266,
title = {A modified serine cycle in Escherichia coli coverts methanol and CO2 to two-carbon compounds},
author = {Yu, Hong and Liao, James C.},
abstractNote = {Microbial utilization of renewable one-carbon compounds, such as methane, methanol, formic acid, and CO2, has emerged as a potential approach to increase the range of carbon sources for bioproduction and address climate change issues. Here, we modify the natural serine cycle present in methylotrophs and build an adapted pathway for Escherichia coli, which allows microorganism to condense methanol (or formate) together with bicarbonate to produce various products. We introduce the modified cycle into E. coli and demonstrate its capability for one-carbon assimilation through growth complementation and isotope labeling experiments. We also demonstrate conversion of methanol to ethanol by utilizing the modified serine cycle in an engineeredE. coli strain, achieving a reaction yet to be accomplished by a one-pot chemical process. This research provides a platform to utilize various renewable one-carbon compounds as carbon sources for biosynthesis through a modified serine cycle in E. coli.},
doi = {10.1038/s41467-018-06496-4},
journal = {Nature Communications},
issn = {2041-1723},
number = 1,
volume = 9,
place = {United States},
year = {2018},
month = {9}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record

Citation Metrics:
Cited by: 2 works
Citation information provided by
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Figures / Tables:

Fig. 1 Fig. 1: Design of the modified serine cycle for E. coli. a Illustration of the natural serine cycle in Methylobacterium extorquens AM1. b Illustration of the modified serine cycle for acetyl-CoA synthesis. Compared to the natural serine cycle (a), the modified serine cycle uses formaldehyde dehydrogenase (Faldh) to simplify themore » oxidation of formaldehyde to formate (blue box), and also utilizes the Agt Sdh combination to avoid hydroxypyruvate as an intermediate in the conversion from glyoxylate to PEP (yellow box). CH2=H4F 5,10-methylene-H4F, Ppc phosphoenolpyruvate carboxylase, Madh malate dehydrogenase, Mtk malate thiokinase, Mcl malyl-CoA lyase, Agt alanine-glyoxylate transaminase, SHMT serine hydroxymethyltransferase, Sdh serine dehydratase, Pps phosphoenolpyruvate synthase, Fthfl formate THF ligase, Mthfs 5,10-methylene-tetrahydrofolate synthase (C1-THF synthase), Medh methanol dehydrogenase, Faldh formaldehyde dehydrogenase, Gpt glutamate-pyruvate transaminase, Gldh glutamate dehydrogenase, Sgt serine-glyoxylate transaminase, Hpr hydroxypyruvate reductase, Gk glycerate kinase, Eno enolase, Fae formaldehyde-activating enzyme, Mtd NADP-dependent methylene-tetrahydromethanopterin/methylene-tetrahydrofolate dehydrogenase, Mch N(5),N(10)-methenyltetrahydromethanopterin cyclohydrolase, Fhc formyltransferase/hydrolase complex, Fch methenyltetrahydrofolate cyclohydrolase« less

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Works referenced in this record:

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    Figures/Tables have been extracted from DOE-funded journal article accepted manuscripts.