Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Logo for

Science 326 (5957): 1263-1268

Copyright © 2009 by the American Association for the Advancement of Science

Impact of Genome Reduction on Bacterial Metabolism and Its Regulation

Eva Yus,1 Tobias Maier,1 Konstantinos Michalodimitrakis,1 Vera van Noort,2 Takuji Yamada,2 Wei-Hua Chen,2 Judith A. H. Wodke,1 Marc Güell,1 Sira Martínez,1 Ronan Bourgeois,1 Sebastian Kühner,2 Emanuele Raineri,1 Ivica Letunic,2 Olga V. Kalinina,2,3 Michaela Rode,2 Richard Herrmann,3 Ricardo Gutiérrez-Gallego,4 Robert B. Russell,2 Anne-Claude Gavin,2 Peer Bork,2,* Luis Serrano1,6

Abstract: To understand basic principles of bacterial metabolism organization and regulation, but also the impact of genome size, we systematically studied one of the smallest bacteria, Mycoplasma pneumoniae. A manually curated metabolic network of 189 reactions catalyzed by 129 enzymes allowed the design of a defined, minimal medium with 19 essential nutrients. More than 1300 growth curves were recorded in the presence of various nutrient concentrations. Measurements of biomass indicators, metabolites, and 13C-glucose experiments provided information on directionality, fluxes, and energetics; integration with transcription profiling enabled the global analysis of metabolic regulation. Compared with more complex bacteria, the M. pneumoniae metabolic network has a more linear topology and contains a higher fraction of multifunctional enzymes; general features such as metabolite concentrations, cellular energetics, adaptability, and global gene expression responses are similar, however.

1 Centre for Genomic Regulation (CRG) and Universitat Pompeu Fabra, Avenida Dr. Aiguader 88, 08003 Barcelona, Spain.
2 European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, D-69117 Heidelberg, Germany.
3 Institute for Information Transmission Problems, Russian Academy of Sciences, Moscow 127994, Russia.
4 Zentrum für Molekulare Biologie Heidelberg (ZMBH), Im Neuenheimer Feld 282, 69120 Heidelberg, Germany.
5 Institut Municipal d’Investigació Médica–Hospital del Mar, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Avenida Dr. Aiguader 88, 08003 Barcelona, Spain.
6 Institució Catalana de Recerca i Estudis Avançats, Lluis Companys 23, Barcelona 08010, Spain.

* To whom correspondence should be addressed. E-mail: luis.serrano{at}, bork{at}

A systems biology tour de force for a near-minimal bacterium.
J. I. Glass, C. A. Hutchison III, H. O. Smith, and J. C. Venter (2014)
Mol Syst Biol 5, 330
   Full Text »    PDF »
A global protein-lipid interactome map.
M. Brehme and M. Vidal (2014)
Mol Syst Biol 6, 443
   Full Text »    PDF »
Transcription start site associated RNAs in bacteria.
E. Yus, M. Guell, A. P. Vivancos, W.-H. Chen, M. Lluch-Senar, J. Delgado, A.-C. Gavin, P. Bork, and L. Serrano (2014)
Mol Syst Biol 8, 585
   Abstract »    Full Text »    PDF »
Cross-talk between phosphorylation and lysine acetylation in a genome-reduced bacterium.
V. van Noort, J. Seebacher, S. Bader, S. Mohammed, I. Vonkova, M. J. Betts, S. Kuhner, R. Kumar, T. Maier, M. O'Flaherty, et al. (2014)
Mol Syst Biol 8, 571
   Abstract »    Full Text »    PDF »
Dissecting the energy metabolism in Mycoplasma pneumoniae through genome-scale metabolic modeling.
J. A. H. Wodke, J. Puchałka, M. Lluch-Senar, J. Marcos, E. Yus, M. Godinho, R. Gutierrez-Gallego, V. A. P. M. dos Santos, L. Serrano, E. Klipp, et al. (2014)
Mol Syst Biol 9, 653
   Abstract »    Full Text »    PDF »
Mapping Condition-Dependent Regulation of Lipid Metabolism in Saccharomyces cerevisiae.
M. C. Jewett, C. T. Workman, I. Nookaew, F. A. Pizarro, E. Agosin, L. I. Hellgren, and J. Nielsen (2013)
g3 3, 1979-1995
   Abstract »    Full Text »    PDF »
Natural Selection for Operons Depends on Genome Size.
P. A. Nunez, H. Romero, M. D. Farber, and E. P. C. Rocha (2013)
Genome Biol Evol 5, 2242-2254
   Abstract »    Full Text »    PDF »
Mycoplasma polysaccharide protects against complement.
J. R. Bolland, W. L. Simmons, J. M. Daubenspeck, and K. Dybvig (2012)
Microbiology 158, 1867-1873
   Abstract »    Full Text »    PDF »
Superessential reactions in metabolic networks.
A. Barve, J. F. M. Rodrigues, and A. Wagner (2012)
PNAS 109, E1121-E1130
   Abstract »    Full Text »    PDF »
Insights into the Gene Expression Profile of Uncultivable Hemotrophic Mycoplasma suis during Acute Infection, Obtained Using Proteome Analysis.
K. M. Felder, P. M. Carranza, P. M. Gehrig, B. Roschitzki, S. Barkow-Oesterreicher, K. Hoelzle, K. Riedel, M. Kube, and L. E. Hoelzle (2012)
J. Bacteriol. 194, 1505-1514
   Abstract »    Full Text »    PDF »
Reconfiguring Regulation.
G. Chalancon, K. Kruse, and M. M. Babu (2012)
Science 335, 1050-1051
   Abstract »    Full Text »    PDF »
Global Network Reorganization During Dynamic Adaptations of Bacillus subtilis Metabolism.
J. M. Buescher, W. Liebermeister, M. Jules, M. Uhr, J. Muntel, E. Botella, B. Hessling, R. J. Kleijn, L. Le Chat, F. Lecointe, et al. (2012)
Science 335, 1099-1103
   Abstract »    Full Text »    PDF »
Characterization of NrnA homologs from Mycobacterium tuberculosis and Mycoplasma pneumoniae.
G. Postic, A. Danchin, and U. Mechold (2012)
RNA 18, 155-165
   Abstract »    Full Text »    PDF »
Expression and Characterization of a Mycoplasma genitalium Glycosyltransferase in Membrane Glycolipid Biosynthesis: POTENTIAL TARGET AGAINST MYCOPLASMA INFECTIONS.
E. Andres, N. Martinez, and A. Planas (2011)
J. Biol. Chem. 286, 35367-35379
   Abstract »    Full Text »    PDF »
The minimal genome--a metabolic and environmental comparison.
M. T. DeWall and D. W. Cheng (2011)
Briefings in Functional Genomics 10, 312-315
   Abstract »    Full Text »    PDF »
Transcriptional response of Mycoplasma genitalium to osmotic stress.
W. Zhang and J. B. Baseman (2011)
Microbiology 157, 548-556
   Abstract »    Full Text »    PDF »
Identification of Lipoprotein MslA as a Neoteric Virulence Factor of Mycoplasma gallisepticum.
S. M. Szczepanek, S. Frasca Jr., V. L. Schumacher, X. Liao, M. Padula, S. P. Djordjevic, and S. J. Geary (2010)
Infect. Immun. 78, 3475-3483
   Abstract »    Full Text »    PDF »
Targeted Chromosomal Knockouts in Mycoplasma pneumoniae.
R. Krishnakumar, N. Assad-Garcia, G. A. Benders, Q. Phan, M. G. Montague, and J. I. Glass (2010)
Appl. Envir. Microbiol. 76, 5297-5299
   Abstract »    Full Text »    PDF »
Excavating the Functional Landscape of Bacterial Cells.
H. Ochman and R. Raghavan (2009)
Science 326, 1200-1201
   Abstract »    Full Text »    PDF »
Proteome Organization in a Genome-Reduced Bacterium.
S. Kuhner, V. van Noort, M. J. Betts, A. Leo-Macias, C. Batisse, M. Rode, T. Yamada, T. Maier, S. Bader, P. Beltran-Alvarez, et al. (2009)
Science 326, 1235-1240
   Abstract »    Full Text »    PDF »
Transcriptome Complexity in a Genome-Reduced Bacterium.
M. Guell, V. van Noort, E. Yus, W.-H. Chen, J. Leigh-Bell, K. Michalodimitrakis, T. Yamada, M. Arumugam, T. Doerks, S. Kuhner, et al. (2009)
Science 326, 1268-1271
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882