Growth and differentiation properties of pikromycin-producing Streptomyces venezuelae ATCC15439

Streptomycetes naturally produce a variety of secondary metabolites, in the process of physiological differentiation. Streptomyces venezuelae differentiates into spores in liquid media, serving as a good model system for differentiation and a host for exogenous gene expression. Here, we report the growth and differentiation properties of S. venezuelae ATCC-15439 in liquid medium, which produces pikromycin, along with genome-wide gene expression profile. Comparison of growth properties on two media (SPA, MYM) revealed that the stationary phase cell viability rapidly decreased in SPA. Submerged spores showed partial resistance to lysozyme and heat, similar to what has been observed for better-characterized S. venezuelae ATCC10712, a chloramphenicol producer. TEM revealed that the differentiated cells in the submerged culture showed larger cell size, thinner cell wall than the aerial spores. We analyzed transcriptome profiles of cells grown in liquid MYM at various growth phases. During transition and/or stationary phases, many differentiationrelated genes were well expressed as judged by RNA level, except some genes forming hydrophobic coats in aerial mycelium. Since submerged spores showed thin cell wall and partial resistance to stresses, we examined cellular expression of MreB protein, an actin-like protein known to be required for spore wall synthesis in Streptomycetes. In contrast to aerial spores where MreB was localized in septa and spore cell wall, submerged spores showed no detectable signal. Therefore, even though the mreB transcripts are abundant in liquid medium, its protein level and/or its interaction with spore wall synthetic complex appear impaired, causing thinner- walled and less sturdy spores in liquid culture.