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Title: Modeling central metabolism and energy biosynthesis across microbial life

Journal Article · · BMC Genomics
 [1];  [2];  [2];  [1];  [2];  [1];  [1]
  1. Argonne National Lab. (ANL), Argonne, IL (United States); Univ. of Chicago, Chicago, IL (United States)
  2. Argonne National Lab. (ANL), Argonne, IL (United States)

Here, automatically generated bacterial metabolic models, and even some curated models, lack accuracy in predicting energy yields due to poor representation of key pathways in energy biosynthesis and the electron transport chain (ETC). Further compounding the problem, complex interlinking pathways in genome-scale metabolic models, and the need for extensive gapfilling to support complex biomass reactions, often results in predicting unrealistic yields or unrealistic physiological flux profiles. As a result, to overcome this challenge, we developed methods and tools to build high quality core metabolic models (CMM) representing accurate energy biosynthesis based on a well studied, phylogenetically diverse set of model organisms. We compare these models to explore the variability of core pathways across all microbial life, and by analyzing the ability of our core models to synthesize ATP and essential biomass precursors, we evaluate the extent to which the core metabolic pathways and functional ETCs are known for all microbes. 6,600 (80 %) of our models were found to have some type of aerobic ETC, whereas 5,100 (62 %) have an anaerobic ETC, and 1,279 (15 %) do not have any ETC. Using our manually curated ETC and energy biosynthesis pathways with no gapfilling at all, we predict accurate ATP yields for nearly 5586 (70 %) of the models under aerobic and anaerobic growth conditions. This study revealed gaps in our knowledge of the central pathways that result in 2,495 (30 %) CMMs being unable to produce ATP under any of the tested conditions. We then established a methodology for the systematic identification and correction of inconsistent annotations using core metabolic models coupled with phylogenetic analysis. In conclusion, we predict accurate energy yields based on our improved annotations in energy biosynthesis pathways and the implementation of diverse ETC reactions across the microbial tree of life. We highlighted missing annotations that were essential to energy biosynthesis in our models. We examine the diversity of these pathways across all microbial life and enable the scientific community to explore the analyses generated from this large-scale analysis of over 8000 microbial genomes.

Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Biological and Environmental Research (BER); National Science Foundation (NSF)
Grant/Contract Number:
AC02-06CH11357
OSTI ID:
1339569
Journal Information:
BMC Genomics, Vol. 17, Issue 1; ISSN 1471-2164
Publisher:
SpringerCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 21 works
Citation information provided by
Web of Science

References (52)

The bacterial cytochrome cbb3 oxidases journal April 2004
Shifts in growth strategies reflect tradeoffs in cellular economics journal January 2009
Biochemistry, evolution and physiological function of the Rnf complex, a novel ion-motive electron transport complex in prokaryotes journal November 2010
Metabolic Capabilities of Escherichia coli: I. Synthesis of Biosynthetic Precursors and Cofactors journal December 1993
Metabolic Capabilities of Escherichia coli II. Optimal Growth Patterns journal December 1993
KEGG: Kyoto Encyclopedia of Genes and Genomes journal January 2000
Optimization based automated curation of metabolic reconstructions journal January 2007
Interactive Tree Of Life (iTOL): an online tool for phylogenetic tree display and annotation journal October 2006
FastTree 2 – Approximately Maximum-Likelihood Trees for Large Alignments journal March 2010
Glycolytic strategy as a tradeoff between energy yield and protein cost journal April 2013
Quantitative prediction of cellular metabolism with constraint-based models: the COBRA Toolbox journal March 2007
SEED Servers: High-Performance Access to the SEED Genomes, Annotations, and Metabolic Models journal October 2012
A Cytochrome bb ′-type Quinol Oxidase in Bacillus subtilis Strain 168 journal November 1999
The RAST Server: Rapid Annotations using Subsystems Technology journal January 2008
Resolving the TCA cycle and pentose-phosphate pathway of Clostridium acetobutylicum ATCC 824: Isotopomer analysis, in vitro activities and expression analysis journal November 2010
ANAEROBIC GROWTH OF A “STRICT AEROBE” ( BACILLUS SUBTILIS ) journal October 1998
Cytochrome o ( bo ) is a proton pump in Paracoccus denitrificans and Escherichia coli journal June 1989
The KEGG databases at GenomeNet journal January 2002
The interaction of oxygen with Propionibacterium acnes journal July 1984
The cost of efficiency in energy metabolism journal May 2013
Bacterial Electron Transport Chains journal June 1988
High-throughput generation, optimization and analysis of genome-scale metabolic models journal August 2010
Glucose dehydrogenase activity in acinetobacter species journal January 1989
Tastes, Structure and Solution Properties of D-Glucono-1,5-lactone journal January 1997
The cytochrome bd respiratory oxygen reductases journal November 2011
Systematic evaluation of objective functions for predicting intracellular fluxes in Escherichia coli journal January 2007
Genetics and Physiology of Acinetobacter journal October 1978
The terminal oxidases of Paracoccus denitrificans journal July 1994
Metabolic costs of amino acid and protein production in Escherichia coli journal July 2013
Microbial genomes and "missing" enzymes: redefining biochemical pathways journal October 1999
Predicting microbial growth journal June 2014
MAFFT version 5: improvement in accuracy of multiple sequence alignment journal January 2005
Formate Production by Streptococcus thermophilus Cultures journal September 1991
The Aerobic and Anaerobic Respiratory Chain of Escherichia coli and Salmonella enterica: Enzymes and Energetics journal June 2014
Control of electron flow in Escherichia coli: coordinated transcription of respiratory pathway genes. journal November 1992
Reduction of aerobic acetate production by Escherichia coli. journal January 1997
Characterization of anaerobic fermentative growth of Bacillus subtilis: identification of fermentation end products and genes required for growth. journal November 1997
Data from: Modeling central metabolism and energy biosynthesis across microbial life dataset August 2016
Systems-Level Metabolic Flux Profiling Elucidates a Complete, Bifurcated Tricarboxylic Acid Cycle in Clostridium acetobutylicum journal November 2011
Systematic evaluation of objective functions for predicting intracellular fluxes in Escherichia coli text January 2007
The variable cytochrome content of Paracoccus Denitrificans grown aerobically under different conditions journal September 1978
Alternative respiratory pathways of Escherichia coli: energetics and transcriptional regulation in response to electron acceptors journal July 1997
Transcriptional profiling of gene expression in response to glucose in Bacillus subtilis: regulation of the central metabolic pathways journal April 2003
Red versus green leaves: transcriptomic comparison of foliar senescence between two Prunus cerasifera genotypes journal February 2020
Nitrate respiration in the actinomycete Streptomyces coelicolor journal February 2005
The Pathway Tools software journal July 2002
Regulation of Carbohydrate Metabolism by Enzyme Competition journal January 1961
Stoichiometric flux balance models quantitatively predict growth and metabolic by-product secretion in wild-type Escherichia coli W3110. journal January 1994
Systems-Level Metabolic Flux Profiling Elucidates a Complete, Bifurcated Tricarboxylic Acid Cycle in Clostridium acetobutylicum journal July 2010
Influence of transport energization on the growth yield of Escherichia coli. journal January 1985
Terminal Oxidases of Bacillus subtilis Strain 168: One Quinol Oxidase, Cytochrome aa3 or Cytochrome bd, Is Required for Aerobic Growth journal December 2000
"Actinobaculum massiliae," a New Species Causing Chronic Urinary Tract Infection journal November 2002

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Methods for automated genome-scale metabolic model reconstruction journal July 2018
Designing Metabolic Division of Labor in Microbial Communities journal April 2019
Using genome-scale metabolic models to compare serovars of the foodborne pathogen Listeria monocytogenes journal June 2018
MODELING THE CORE METABOLISM OF Komagataeibacter hansenii ATCC 23769 TO EVALUATE NANOCELLULOSE BIOSYNTHESIS journal September 2018
Unraveling Core Functional Microbiota in Traditional Solid-State Fermentation by High-Throughput Amplicons and Metatranscriptomics Sequencing journal July 2017
Bio-Inspired Silver Nanoparticles Impose Metabolic and Epigenetic Toxicity to Saccharomyces cerevisiae journal September 2019
Data from: Modeling central metabolism and energy biosynthesis across microbial life dataset August 2016