Pleiotropic Effects of a Butyrolaetone-type Autoregulator on Mutants of Streptomyces griseus Blocked in Cytodifferentiation

Abstract

Mutants of Streptomyces griseus blocked in cytodifferentiation regained their capacity to form differentiated mycelia and/or anthracycline pigments in the presence of butyrolactonetype autoregulatory effectors such as trans-2-(6'-methylheptanol-l '-yl)-3-hydroxymethy1-4-butanolide. In the pertinent indicator strains, the effect has been correlated with the increase of lipid synthesis, with changes in the composition of lipid fraction and with the restoration of the production of neutral proteinases. The results suggest that autoregulatory butyrolactones from streptomycetes stimulate cytodifferentiation of their producers at an early stage of development.

Metabolic initiation of differentiation and secondary metabolism by Streptomyces griseus: significance of the stringent response (ppGpp) and GTP content in relation to A factor

“…The mechanisms involved in this phenomenon remain unknown, but it may imply widespread pleiotropic effects of the gene(s) determining A-factor synthesis of S. griseus. Since A factor alone could not initiate aerial mycelium formation in the presence of excess nutrients, it may have a role in making the cells competent to adapt to environmental changes, as suggested earlier by Grafe et al (9). The remarkable synergistic effect produced by the combination of decoyinine and A factor ( …”

Synergistic effect of cobalt on the induction by A‐factor of the formation of aerial mycelium and anthracyclines by a blocked mutant of Streptomyces griseus

“…1982. Concomitant with the appearance of the parental phenotype during both surface and submerged cultivations, mutant strains 86 and 15 of the antracycline-producing parents 8. griseus JA 5142 and JA 3933 exhibited noticeable biochemical alterations (GRAFE et al 1984a(GRAFE et al , 1984b. These changes could, however, not elucidate the initial mechanism of action of l a .…”

Effect of γ‐butyrolactone derivative on an artificial membrane

“…Thus mutant strains incapable of producing I or II did not form both aerial mycelium nd antibiotics such as streptomycin or daunomycin but responded to the administration of low amounts of these autoregulators to the growth medium with full reconstitution of sporulation and/or secondary metabolism [4,5]. Though the morphological and biochemical changes induced by I or II in the pertinent blocked mutants of S. griseus have been studied [5,6], the initial site of action of these inducers of cytodifferentiation still remains to be elucidated. It has been suggested that I chelates cations essential for cytodifferentiation, particularly the cobalt, and transports them through the cytoplasmic Scheme I membrane as a lipophilic carrier [6].…”

“…I or II (for structures see scheme 1) are needed as endogenous regulatory molecules for normal cytodifferentiation of some strains of Streptomyces griseus [ 1,4]. Thus mutant strains incapable of producing I or II did not form both aerial mycelium nd antibiotics such as streptomycin or daunomycin but responded to the administration of low amounts of these autoregulators to the growth medium with full reconstitution of sporulation and/or secondary metabolism [4,5]. Though the morphological and biochemical changes induced by I or II in the pertinent blocked mutants of S. griseus have been studied [5,6], the initial site of action of these inducers of cytodifferentiation still remains to be elucidated.…”