A Lot of alkalophilic actinomycetes were isolated from alkaline soil samples collected at Yunnan, China using a number of different media adjusted to pH 10. Forty nine isolates and 10 type strains of the genus Streptomyces were selected for studying their physiological, biochemical, morphological and chemotaxonomic characteristics, and a cluster analysis based on their 82 unit characters was carried out. DNA-DNA homology among 9 strains selected from each cluster was determined. Characteristics of the alkalophilic actinomycetes and relationship between the alkalophilic and non-alkalophilic actinomycetes were discussed.
A microbial hormone, A-factor, controls streptomycin production, streptomycin resistance, and aerial mycelium formation in Streptomyces griseus. A-factor exerts its regulatory role by binding to a specific receptor protein which, in the absence of A-factor, acts as a repressor-type regulator for these morphological and physiological differentiation. In the signal relay leading to streptomycin production, the A-factor signal is transmitted from the A-factor receptor to the upstream activation sequence of a regulatory gene, strR, in the streptomycin biosynthetic gene cluster via an A-factor-dependent protein that acts as a transcription factor for strR. The signal relay leading to aerial mycelium formation includes proteins similar to response regulators of the procaryotic two-component regulatory systems and to a family of membrane translocators engaged in ATP-dependent secretion mechanisms. Accumulating data show that a large family of γ-butyrolactones act as autoregulators in a wide variety of Streptomyces spp. In addition to the hormonal control by the autoregulators, secondary metabolism and morphogenesis are controlled by signal transduction systems via both procaryotic and eucaryotic protein kinases. A pair of the AfsQ1 and AfsQ2 proteins constituting a procaryotic-type histidine-aspartate phosphotransfer system globally controls secondary metabolite formation in Streptomyces coelicolor A3(2). Another pair of proteins, AfsK and AfsR, which also serves as a global regulator for secondary metabolism in S. coelicolor, constitutes an eucaryotic-type phosphotransfer system in which a protein serine/threonine/tyrosine kinase AfsK phosphorylates serine and threonine residues of AfsR. A wide distribution of DNA sequences homologous with the afsQ1/afsQ2 and afsK/afsR genes suggests that both procaryotic and eucaryotic protein kinases control secondary metabolism in general in Streptomyces. Inhibition by K-252a and staurosporine, known as eucaryotic protein kinase inhibitors, of antibiotic production and aerial mycelium formation of S. griseus and S. coelicolor supports this idea.
We surveyed the research activity on antibiotic screening over the last 10 years using data published in the Journal of Antibiotics (1984∼1993) and the Japan Kokai Patent (1983∼1992). Research on new antibiotic screening is very active in Japan, and we considered a survey of these data to be helpful in grasping domestic and international research trends in this field. In this report, we use the term “antibiotics” not in the narrow sense of antimicrobial antibiotics, but rather to mean bioactive microbial products.
ES-242-1, a novel bioxanthracene, is the first microbial compound found to act with a novel mechanism of action on the N-methyl-D-aspartate (NMDA) receptor and may possess neuroprotective properties useful in the treatment of disease involving glutamate toxicity. HS-142-1 is the first compound to be discovered as a specific antagonist for functional receptors for natriuretic peptide; the compound would be useful to clarify the physiological and pathophysiological functions of natriuretic peptides. The protein kinase inhibitor K-252a was recently reported to potentiate the activity of a neurotrophin and to promote some neuronal survival. K-252a and its derivatives would be lead compounds for the development of compounds therapeutically useful in the treatment of neurological disease and injury.
Self-defense genes of fortimicin (Fm)-group antibiotic producers varied between genera, and can be classified into two groups regarding to their resistance profiles and DNA homologies. DNA sequence analyses revealed that the resistance genes of the Streptomyces and Saccharopolyspora producers encode methyltransferases capable of modifying 16S rRNA as same as kamB of a nebramycin producer, Streptomyces tenebrarius, and that those of the Micromonospora and Dactylosporangium producers encode another type of 16S rRNA methyltransferases similar to grmA of a gentamicin producer, Micromonospora purpurea. A Fm-A producer, Micromonospora olivasterospora, transformed by the Fm-resistance gene (fmrT) of Streptomyces tenjimariensis showed significant increase of the resistance level to Fm-A. This result indicated that heterologous genes from producers of the structurally related antibiotics are useful as DNA sources for the molecular breeding of antibiotic producers.