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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}crg.es, bork{at}embl.de

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