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Science 9 October 2009:
Vol. 326. no. 5950, pp. 252 - 257
DOI: 10.1126/science.1174094

Research Articles

Reactome Array: Forging a Link Between Metabolome and Genome

Ana Beloqui,1,* María-Eugenia Guazzaroni,1,* Florencio Pazos,2 José M. Vieites,1 Marta Godoy,2 Olga V. Golyshina,3 Tatyana N. Chernikova,3 Agnes Waliczek,3 Rafael Silva-Rocha,2 Yamal Al-ramahi,1 Violetta La Cono,4 Carmen Mendez,5 José A. Salas,5 Roberto Solano,2 Michail M. Yakimov,4 Kenneth N. Timmis,3,6 Peter N. Golyshin,3,7,8,{dagger},{ddagger} Manuel Ferrer1,{dagger},{ddagger}

We describe a sensitive metabolite array for genome sequence–independent functional analysis of metabolic phenotypes and networks, the reactomes, of cell populations and communities. The array includes 1676 dye-linked substrate compounds collectively representing central metabolic pathways of all forms of life. Application of cell extracts to the array leads to specific binding of enzymes to cognate substrates, transformation to products, and concomitant activation of the dye signals. Proof of principle was shown by reconstruction of the metabolic maps of model bacteria. Utility of the array for unsequenced organisms was demonstrated by reconstruction of the global metabolisms of three microbial communities derived from acidic volcanic pool, deep-sea brine lake, and hydrocarbon-polluted seawater. Enzymes of interest are captured on nanoparticles coated with cognate metabolites, sequenced, and their functions unequivocally established.

1 CSIC, Institute of Catalysis, 28049 Madrid, Spain.
2 CSIC, Centro Nacional de Biotecnología, 28049 Madrid, Spain.
3 HZI-Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany.
4 Institute for Coastal Marine Environment, CNR, Messina 98122, Italy.
5 Universidad de Oviedo, 33006 Oviedo, Spain.
6 Institute of Microbiology, Carolo-Wilhelmina Technical University of Braunschweig, 38106 Braunschweig, Germany.
7 School of Biological Sciences, Bangor University, Gwynedd LL572 UW, UK.
8 Centre for Integrated Research in the Rural Environment, Aberystwyth University-Bangor University Partnership (CIRRE).

* These authors contributed equally to this work.

{dagger} These authors contributed equally to this work.

{ddagger} To whom correspondence should be addressed. E-mail: mferrer{at}icp.csic.es (M.F.); p.golyshin{at}bangor.ac.uk (P.N.G.)

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Science. ISSN 0036-8075 (print), 1095-9203 (online)