Microbial Physiology and Genomics

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.