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Nat Rev Microbiol. 2005 Jul;3(7):557-65.

Metabolic footprinting and systems biology: the medium is the message.

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School of Chemistry, University of Manchester, Faraday Building, PO Box 88, Sackville Street, Manchester M60 1QD, UK.


One element of classical systems analysis treats a system as a black or grey box, the inner structure and behaviour of which can be analysed and modelled by varying an internal or external condition, probing it from outside and studying the effect of the variation on the external observables. The result is an understanding of the inner make-up and workings of the system. The equivalent of this in biology is to observe what a cell or system excretes under controlled conditions - the 'metabolic footprint' or exometabolome - as this is readily and accurately measurable. Here, we review the principles, experimental approaches and scientific outcomes that have been obtained with this useful and convenient strategy.

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