TY - JOUR

T1 - Methane utilization in Methylomicrobium alcaliphilum 20ZR

T2 - A systems approach

AU - Akberdin, Ilya R.

AU - Thompson, Merlin

AU - Hamilton, Richard

AU - Desai, Nalini

AU - Alexander, Danny

AU - Henard, Calvin A.

AU - Guarnieri, Michael T.

AU - Kalyuzhnaya, Marina G.

N1 - Publisher Copyright: © 2018 The Author(s).

PY - 2018/2/6

Y1 - 2018/2/6

N2 - Biological methane utilization, one of the main sinks of the greenhouse gas in nature, represents an attractive platform for production of fuels and value-added chemicals. Despite the progress made in our understanding of the individual parts of methane utilization, our knowledge of how the whole-cell metabolic network is organized and coordinated is limited. Attractive growth and methane-conversion rates, a complete and expert-annotated genome sequence, as well as large enzymatic, 13C-labeling, and transcriptomic datasets make Methylomicrobium alcaliphilum 20ZR an exceptional model system for investigating methane utilization networks. Here we present a comprehensive metabolic framework of methane and methanol utilization in M. alcaliphilum 20ZR. A set of novel metabolic reactions governing carbon distribution across central pathways in methanotrophic bacteria was predicted by in-silico simulations and confirmed by global non-targeted metabolomics and enzymatic evidences. Our data highlight the importance of substitution of ATP-linked steps with PPi-dependent reactions and support the presence of a carbon shunt from acetyl-CoA to the pentose-phosphate pathway and highly branched TCA cycle. The diverged TCA reactions promote balance between anabolic reactions and redox demands. The computational framework of C1-metabolism in methanotrophic bacteria can represent an efficient tool for metabolic engineering or ecosystem modeling.

AB - Biological methane utilization, one of the main sinks of the greenhouse gas in nature, represents an attractive platform for production of fuels and value-added chemicals. Despite the progress made in our understanding of the individual parts of methane utilization, our knowledge of how the whole-cell metabolic network is organized and coordinated is limited. Attractive growth and methane-conversion rates, a complete and expert-annotated genome sequence, as well as large enzymatic, 13C-labeling, and transcriptomic datasets make Methylomicrobium alcaliphilum 20ZR an exceptional model system for investigating methane utilization networks. Here we present a comprehensive metabolic framework of methane and methanol utilization in M. alcaliphilum 20ZR. A set of novel metabolic reactions governing carbon distribution across central pathways in methanotrophic bacteria was predicted by in-silico simulations and confirmed by global non-targeted metabolomics and enzymatic evidences. Our data highlight the importance of substitution of ATP-linked steps with PPi-dependent reactions and support the presence of a carbon shunt from acetyl-CoA to the pentose-phosphate pathway and highly branched TCA cycle. The diverged TCA reactions promote balance between anabolic reactions and redox demands. The computational framework of C1-metabolism in methanotrophic bacteria can represent an efficient tool for metabolic engineering or ecosystem modeling.

KW - CONSTRAINT-BASED MODELS

KW - METHANOTROPHIC BACTERIUM

KW - PHOSPHOKETOLASE PATHWAY

KW - GENUS METHYLOMICROBIUM

KW - BIOCHEMICAL-PROPERTIES

KW - ESCHERICHIA-COLI

KW - LIQUID FUELS

KW - METABOLISM

KW - PYROPHOSPHATE

KW - GROWTH

UR - http://www.scopus.com/inward/record.url?scp=85041644582&partnerID=8YFLogxK

U2 - 10.1038/s41598-018-20574-z

DO - 10.1038/s41598-018-20574-z

M3 - Article

C2 - 29410419

AN - SCOPUS:85041644582

VL - 8

SP - 2512

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

M1 - 2512

ER -