Conservation of the metabolomic response to starvation across two divergent microbes

doi:10.1073/pnas.0609508103

Conservation of the metabolomic response to starvation across two divergent microbes

*Lewis Sigler Institute for Integrative Genomics and
Departments of ^†Molecular Biology and
^‡Chemistry, Princeton University, Princeton, NJ 08544

Contributed by David Botstein, October 26, 2006 (received for review September 24, 2006)

Abstract

We followed 68 cellular metabolites after carbon or nitrogen starvation of Escherichia coli and Saccharomyces cerevisiae, using a filter-culture methodology that allows exponential growth, nondisruptive nutrient removal, and fast quenching of metabolism. Dynamic concentration changes were measured by liquid chromatography–tandem mass spectrometry and viewed in clustered heat-map format. The major metabolic responses anticipated from metabolite-specific experiments in the literature were observed as well as a number of novel responses. When the data were analyzed by singular value decomposition, two dominant characteristic vectors were found, one corresponding to a generic starvation response and another to a nutrient-specific starvation response that is similar in both organisms. Together these captured a remarkable 72% of the metabolite concentration changes in the full data set. The responses described by the generic starvation response vector (42%) included, for example, depletion of most biosynthetic intermediates. The nutrient-specific vector (30%) included key responses such as increased phosphoenolpyruvate signaling glucose deprivation and increased α-ketoglutarate signaling ammonia deprivation. Metabolic similarity across organisms extends from the covalent reaction network of metabolism to include many elements of metabolome response to nutrient deprivation as well.

Footnotes

^§To whom correspondence may be addressed. E-mail: botstein{at}princeton.edu or joshr{at}princeton.edu
Author contributions: M.J.B., J.Y., B.D.B., D.B., and J.D.R. designed research; M.J.B., J.Y., B.D.B., W.L., E.K., and J.D.R. performed research; M.J.B. and J.D.R. contributed new reagents/analytic tools; M.J.B., J.Y., B.D.B., W.L., D.B., and J.D.R. analyzed data; and M.J.B., D.B., and J.D.R. wrote the paper.
The authors declare no conflict of interest.
This article contains supporting information online at www.pnas.org/cgi/content/full/0609508103/DC1.
↵ ¶ For fixed pathway flux, a larger pool results in slower labeling (16); accordingly, the decreased rate of labeling in the nitrogen-starved cells can be attributed largely to the larger pool size.
Abbreviations:

FBP,

fructose-1,6-bisphosphate;

PEP,

phosphoenolpyruvate;

SVD,

singular value decomposition;

TCA,

tricarboxylic acid.
Freely available online through the PNAS open access option.