Identification of the leucine-to-2-methylbutyric acid catabolic pathway of Lactococcus lactis

Balasubramanian Ganesan, Piotr Dobrowolski, Bart C Weimer

Research output: Contribution to journalArticle

46 Scopus citations

Abstract

Nutrient starvation and nonculturability in bacteria lead to changes in metabolism not found during the logarithmic phase. Substrates alternate to those used during growth are metabolized in these physiological states, yielding secondary metabolites. In firmicutes and actinobacteria, amino acid catabolic pathways are induced during starvation and nonculturability. Examination of lactococci showed that the population entered a nonculturable state after carbohydrate depletion and was incapable of growth on solid media; however, the cells gained the ability to produce branched-chain fatty acids from amino acids. Gene expression profiling and in silico pathway analysis coupled with nuclear magnetic resonance spectroscopy were used to delineate the leucine catabolic pathway. Lactococci produced acetic and propionic acid during logarithmic growth and starvation. At the onset of nonculturability, 2-methylbutyric acid was produced via hydroxymethyl-glutaryl-coenzyme A (CoA) and acetyl-CoA, along with ATP and oxidation/reduction precursors. Gene expression profiling and genome sequence analysis showed that lactococci contained redundant genes for branched-chain fatty acid production that were regulated by an unknown mechanism linked to carbon metabolism. This work demonstrated the ability of a firmicute to induce new metabolic capabilities in the nonculturable state for producing energy and intermediates needed for transcription and translation. Phylogenetic analyses showed that homologues of these enzymes and their functional motifs were widespread across the domains of life.

Original languageEnglish (US)
Pages (from-to)4264-4273
Number of pages10
JournalApplied and Environmental Microbiology
Volume72
Issue number6
DOIs
StatePublished - Jun 2006
Externally publishedYes

ASJC Scopus subject areas

  • Environmental Science(all)
  • Biotechnology
  • Microbiology

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