skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Modeling central metabolism and energy biosynthesis across microbial life

Abstract

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 ATPmore » 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.« less

Authors:
 [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)
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23); National Science Foundation (NSF)
OSTI Identifier:
1339569
Grant/Contract Number:  
AC02-06CH11357
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
BMC Genomics
Additional Journal Information:
Journal Volume: 17; Journal Issue: 1; Journal ID: ISSN 1471-2164
Publisher:
Springer
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Edirisinghe, Janaka N., Weisenhorn, Pamela, Conrad, Neal, Xia, Fangfang, Overbeek, Ross, Stevens, Rick L., and Henry, Christopher S. Modeling central metabolism and energy biosynthesis across microbial life. United States: N. p., 2016. Web. doi:10.1186/s12864-016-2887-8.
Edirisinghe, Janaka N., Weisenhorn, Pamela, Conrad, Neal, Xia, Fangfang, Overbeek, Ross, Stevens, Rick L., & Henry, Christopher S. Modeling central metabolism and energy biosynthesis across microbial life. United States. doi:10.1186/s12864-016-2887-8.
Edirisinghe, Janaka N., Weisenhorn, Pamela, Conrad, Neal, Xia, Fangfang, Overbeek, Ross, Stevens, Rick L., and Henry, Christopher S. Mon . "Modeling central metabolism and energy biosynthesis across microbial life". United States. doi:10.1186/s12864-016-2887-8. https://www.osti.gov/servlets/purl/1339569.
@article{osti_1339569,
title = {Modeling central metabolism and energy biosynthesis across microbial life},
author = {Edirisinghe, Janaka N. and Weisenhorn, Pamela and Conrad, Neal and Xia, Fangfang and Overbeek, Ross and Stevens, Rick L. and Henry, Christopher S.},
abstractNote = {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.},
doi = {10.1186/s12864-016-2887-8},
journal = {BMC Genomics},
number = 1,
volume = 17,
place = {United States},
year = {Mon Aug 08 00:00:00 EDT 2016},
month = {Mon Aug 08 00:00:00 EDT 2016}
}

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

Citation Metrics:
Cited by: 2 works
Citation information provided by
Web of Science

Save / Share: