A systems level predictive model for global gene regulation of methanogenesis in a hydrogenotrophic methanogen
- Sung Ho Yoon1,4,
- Serdar Turkarslan1,
- David J. Reiss1,
- Min Pan1,
- June A. Burn2,
- Kyle C. Costa2,
- Thomas J. Lie2,
- Joseph Slagel1,
- Robert L. Moritz1,
- Murray Hackett3,
- John A. Leigh2,5 and
- Nitin S. Baliga1,5
- 1Institute for Systems Biology, Seattle, Washington 98109, USA;
- 2Department of Microbiology, University of Washington, Seattle, Washington 98195, USA;
- 3Department of Chemical Engineering, University of Washington, Seattle, Washington 98195, USA;
- 4Korea Research Institute of Bioscience & Biotechnology, Daejeon 305-806, Republic of Korea
Abstract
Methanogens catalyze the critical methane-producing step (called methanogenesis) in the anaerobic decomposition of organic matter. Here, we present the first predictive model of global gene regulation of methanogenesis in a hydrogenotrophic methanogen, Methanococcus maripaludis. We generated a comprehensive list of genes (protein-coding and noncoding) for M. maripaludis through integrated analysis of the transcriptome structure and a newly constructed Peptide Atlas. The environment and gene-regulatory influence network (EGRIN) model of the strain was constructed from a compendium of transcriptome data that was collected over 58 different steady-state and time-course experiments that were performed in chemostats or batch cultures under a spectrum of environmental perturbations that modulated methanogenesis. Analyses of the EGRIN model have revealed novel components of methanogenesis that included at least three additional protein-coding genes of previously unknown function as well as one noncoding RNA. We discovered that at least five regulatory mechanisms act in a combinatorial scheme to intercoordinate key steps of methanogenesis with different processes such as motility, ATP biosynthesis, and carbon assimilation. Through a combination of genetic and environmental perturbation experiments we have validated the EGRIN-predicted role of two novel transcription factors in the regulation of phosphate-dependent repression of formate dehydrogenase—a key enzyme in the methanogenesis pathway. The EGRIN model demonstrates regulatory affiliations within methanogenesis as well as between methanogenesis and other cellular functions.
Footnotes
-
↵5 Corresponding authors
E-mail Nitin.Baliga{at}systemsbiology.org
E-mail leighj{at}u.washington.edu
-
[Supplemental material is available for this article.]
-
Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.153916.112.
Freely available online through the Genome Research Open Access option.
- Received December 19, 2012.
- Accepted July 29, 2013.
This article, published in Genome Research, is available under a Creative Commons License (Attribution-NonCommercial 3.0 Unported), as described at http://creativecommons.org/licenses/by-nc/3.0/.