Quantitative proteome analysis of Streptomyces coelicolor Nonsporulating liquid cultures demonstrates a complex differentiation process comparable to that occurring in sporulating solid cultures.

Streptomyces species produce many clinically important secondary metabolites and present a complex developmental cycle that includes programmed cell death (PCD) phenomena and sporulation. Industrial fermentations are usually performed in liquid cultures, conditions in which Streptomyces strains generally do not sporulate, and it was traditionally assumed that no differentiation took place. Recently, the existence of an early compartmentalized mycelium (MI) and a later multinucleated mycelium (MII) were described in solid and liquid cultures. The aim of this work was to compare the proteomes of the different developmental stages in liquid and solid S. coelicolor cultures, in order to give new insights in Streptomyces biology, and improve industrial fermentations. Using iTRAQ labeling and LC-MS/MS analysis of peptides, we demonstrate that differentiation in S. coelicolor liquid cultures is comparable to solid cultures. Eighty-three percent of all the identified proteins showed similar abundance values in MI and MII from liquid and solid cultures. Proteins involved in secondary metabolism (actinorhodin and type II polyketide biosynthesis, beta-lactamases, epimerases) were up-regulated in MII. Proteins involved in primary metabolism (ribosome, Krebs cycle, and energy production) were detected in greater abundance in MI. The most remarkable protein abundance differences between MII from solid and liquid cultures were associated with the final stages of hyphae compartmentalization and spore formation.