Inducers of both cytodifferentiation and anthracycline biosynthesis of Streptomyces griseus and their occurrence in actinomycetes and other microorganisms

Abstract

Many taxonomically different strains of actinomycetes as well as several other procaryotic and eucaryotic microorganisms were shown t o produce inducers of cytodifferentiation and anthracycline biosynthesis being active towards blocked mutant ZIMET 43682 of Streptomyces griseus. 37 out of 40 strains of the species of S. griseus (92.5%) yielding different kinds of antibiotics were able to induce both the formation of aerial mycelium in theindicator strain ZIMET 43682 concomitant with the biosynthesis of anthracycline antibiotics. 80 (26.3%) out of 304 strains belonging to 94 different Streptomyces species were also producers of inducing agents. Among 77 strains of actinomycetes belonging to 28 different genera being apart from Streptomyees, 12 strains displayed inducing activity (15.6%). The results obtained so far support the conclusion that the formation of inducing agents was neither associated with a particular species of Styeptomyces nor its capacity to produce a given antibiotic. The occurrence of inducers has been observed even with members of other genera. Few strains were capable of inducing only one of the differentiation-associated functions. Some strains of Strept0nzyce.s species produced a t least two different kinds of inducers discernible by their Rf values on TLC.Microorganisms can produce low-molecular weight substances, autoregulators, or bioreguIators (KHOKHLOV 1982), which can take part in the regulation of cytodifferentiation and antibiotic biosynthesis as so-called triggers. Occasionally, very low concentrations of the pertinent effector molecules are secreted into the medium where they play a role as a signal affecting, for instance in streptomycetes, not only the formation of antibiotics but also of aerial mycelium and spores. As it has been shown by KHOKHLOV (1982) and ERITT et al. (1982), mutants of streptomycetes can be isolated which are blocked in the biosynthesis of autoregulators, and being unable both to sporulate and to express other differentiation-associated functions. But in the presence of autoregulatory effectors as e.g. 25-(6'-methylheptanoy1)-3S-hydroxymethyl-4-butanolide (A-factor) (KLEINER et aE. 1976) these mutant strains regained their capacity to differentiate, again (KHOKHLOV 1982 b, GRAFE and ERITT 1983. Recently, we demonstrated that anthracycline-producing strains of Streptomyces griseus (ZIMET 43668 and ZIMET 43689) can secrete a substance related in its constitution to A-factor (GRAFE and ERITT 1983), and that the blocked mutant ZIMET 43682 responded to this effector with the onset of lenkaemomycin biosynthesis and formation of aerial niycelia.In the present communication we report on the results of our screening for similar compounds among actinomycetes and other microorganisms by the use of the above indicator mutant ZIMET 43682. The aim of this work was to answer the question: is the production of autoregulatory substances specifically related to the parental strain ZIMET 43689 or can they also be generated by other, even taxononiically different, strains, ...

Deoxyriboendonucleases with exocytoplasmic location in Streptomyces

“…Additional factors that affect differentiation, not present in submerged culture (e.g. dryness, nutritionally defined microenvironment or affecting diffusible bioregulators ] Khoklov et al 1973;Kalakoutskii and Agre 1976;Ensign 1978;Bir6 et al 1980;Eritt et al 1984;Kondo et al 1988]) could also intervene in surface cultures to promote nuclease synthesis in S. albus G and, possibly, in general in Streptomyces.…”

Production of butyrolactone autoregulators by Streptomyces coelicolor A3(2)

“…Furthermore, A‐factor active compound(s) have been reported to have no function in this strain in either morphological differentiation or antibiotic production, because a mutant lacking the ability to produce A‐factor active compound(s) showed no defects in antibiotic production or morphological differentiation [14]. However, from the widely varying capacities for butyrolactone autoregulator production among Streptomyces species [15, 16], we suspect that S. coelicolor A3(2) may produce other types of butyrolactone autoregulators, such as VB or IM‐2 types, and that in this strain these types might act as signal molecules to trigger morphological differentiation.…”

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

“…related to I have been generated by many other, even taxonomically different, streptomycetes (Eritt et al, , 1984Grafe et al, 19826;1983a). In the present work we studied the effect of one of these interspecific inducer molecules, tran~-2-(6'-methylheptanol-1 '-yl)-3-hydroxymethyl-4-butanolide (11), on the development of submerged cultures of blocked mutants of anthracycline-producing strains of S. griseus incapable of producing the endogenous signal compound I.…”