Marie Joelle Virolle
University Paris Sud, France
Title: Strong antibiotic production is correlated with an oxidative metabolism in Streptomyces
Biography
Biography: Marie Joelle Virolle
Abstract
The Streptomyces genus is well known for its outstanding ability to produce secondary metabolites of great interest for human kind
such as antibiotics. Antibiotic biosynthesis occurs in the periods of slow or no growth and is triggered by phosphate limitation, a
condition known to be correlated with energetic stress. However, the metabolic changes underlying the transition between primary
and secondary metabolism remains largely elusive. Comparative physiological and proteomic studies of two closely related model
strains, S. lividans and S. coelicolor, weak and strong producers of the same antibiotics, respectively, were carried out. These studies
clarified for the first time the nature of the metabolic transition between primary and secondary metabolism. This switch triggered
by energetic stress results from a transition from a glycolytic to an oxidative metabolism in order to restore the energetic balance of
the cell. Our results indicate that in condition of energetic stress, the acetyl-CoA generated by glycolysis, rather than being stored as
lipids of the triacylglycerol family, is used to fuel the Krebs cycle, more favorable than glycolysis for energy generation. Krebs cycle
yields molecules that are direct precursors of amino acids used for peptidyl antibiotic biosynthesis as long as sufficient nitrogen is
available. When nitrogen becomes limiting, acetyl-CoA would then be used for direct biosynthesis of polyketide antibiotics. A tool
based on these novel principles was conceived and implemented to enhance the expression of the numerous biosynthetic pathways
present in the Streptomyces genomes.