Secondary metabolism in actinomycetes is brought on by exhaustion of a nutrient and/or by a growth rate decrease. These events generate signals which effect a cascade of regulatory events resulting in chemical differentiation (secondary metabolism) and morphological differentiation (morphogenesis). The signal is often a low molecular weight butyrolactone inducer (autoregulatory factor) which acts by negative control, i.e. by binding to a regulatory protein (repressor protein / receptor protein) which prevents secondary metabolism and morphogenesis during rapid growth and nutrient sufficiency. Nutrient/growth rate signals presumably activate a “master gene” which either acts at the level of translation by encoding a rare tRNA, or by encoding a positive transcription factor. Such master genes control both secondary metabolism and morphogenesis. At the second level of regulatory hierarchy are genes which control one branch of the cascade, i.e. either secondary metabolism or morphogenesis but not both. In the secondary metabolism branch, genes at the third level control formation of particular groups of secondary metabolites. At the fourth level are genes which control smaller groups, and finally, fifth level genes control individual biosynthetic pathways; these are usually positively acting but at least one acts negatively. These are also several levels of hierarchy on the morphogenesis branch. The second level includes genes which control aerial mycelium formation plus all the conidial genes lower in the cascade. Each third level locus controls a particular stage of conidiation (e.g. coiling, septation, wall thickening, spore maturation or spore pigmentation). Many of the these conidiation loci are complex, containing a number of genes; at least two code for sigma factors. Feedback regulation also plays a role in secondary metabolite control.

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Streptomyes tendae Tü 901/8c produces several secondary metabolites originating from different biosynthetic pathways, namely the nikkomycins, ketomycin, chlorothricin and the juglomycins. The significance of the stringent response in the induction of the nikkomycin production during different growth rates in continuous culture and batch fermentations was investigated. Merely, after nutritional shift down into chemically defined medium the strain exhibited a stringent response with two accompanying intracellular accumulations of ppGpp. This was found to be due to different consumption rates of some intracellular amino acids and dependent on relA functions. A relaxed mutant with a reduced ability to accumulate ppGpp, also with respect to the second accumulation observed, failed to produce nikkomycins.

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Streptomyces griseus does not sporulate when grown in a nutrient rich medium. Two mutants that sporulate in such media were isolated and characterized. The mutants sporulate at the same time as the wildtype when grown in a nutrient poor medium. The mutants and wildtype exhibit the same commitment to sporulation following a nutritional shiftdown. Six genomic DNA fragments of wildtype cells when transformed into the mutants caused these mutants to acquire the wildtype phenotype of not sporulating in rich growth media. Restriction analyses show that the six cloned DNA fragments are different. The six clones suppressed sporulation when transformed into Streptomyces coelicolor and Streptomyces lividans and secondary metabolite production was suppressed in S. coelicolor.

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A mutant of Streptomyces griseus, NY5, differs from the parent in sporulating when grown in a nutrient rich growth medium. Cloned genes of the wildtype organism in the multicopy plasmid pIJ702 transformed into the NY5 mutant cells resulted in converting the mutant phenotype of sporulating in rich medium to the parental genotype of not sporulating in rich medium. A 1.5 kb DNA fragment was sequenced and found to contain two open reading frame gene regions. Restriction deletion mapping and subcloning revealed a gene which when transformed in high copy number into S. griseus wildtype, mutant NY5 and S. lividans resulted in suppression of sporulation and fragmented cell growth. The gene, named ssgA (DDJB/EMBL/GenBank accession no. is D50051), encodes a 145 amino acid protein with a calculated size of 15.8 kDa. The predicted protein has a strong negative charge and shows no significant sequence homology to known proteins. Southern analysis detected regions in S. coelicolor and S. lividans DNA homologous to ssgA.

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The motility and chemotactic behavior of the soil actinomycete Catenuloplanes japonicus IFO 14176 was studied. The mature growth on the humic acid-vitamin agar medium exhibited the abundant formation of dichotomously branched aerial hyphae, from which motile, flagellated spores, or zoospores, were released upon immersion into a 10⁻² M phosphate buffer (pH 7.0) containing 10% soil extract. A quantitative microcapillary assay revealed that the zoospores are significantly attracted to a variety of organic compounds common to the soil environments. Monosaccharides such as L-arabinose, D-xylose, D-glucose and D-galactose served as positive chemoattractants at considerably low concentrations; the maximum responses to the compounds occurred at 10⁻⁵ to 10⁻³ M, and the thresholds were 10⁻⁶ to 10⁻⁵ M. Amino acids (D-alanine, L-glutamate, and L-proline), aromatic compounds (vanillin, vanillate, protocatechuate, and myricetin), uronic acid (α-D-galacturonate) and amino sugars (D-glucosamine, and N-acetyl-D-glucosamine) all elicited concentration-dependent positive responses within the range of 10⁻⁴ to 10⁻¹ M. Of the tested compounds, vanillin at 10⁻¹ M provided the strongest response. The chemotactic activities of C. japonicus should tend to bring it toward the appropriate ecological locations where concentrated food sources are present. The Palleroni chemotactic method based on the 10⁻¹ M-vanillin attraction achieved the selective isolation of Catenuloplanes spp. from natural soil samples

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Taxonomy of two new actinomycete strains, which were isolated from a decayed leaf and a root of herbaceous plant, was studied. The organisms had branched substrate mycelia and chains of arthrospores on aerial mycelia. Cell walls of both strains contained meso-diaminopimelic acid and whole-cells contained madurose as a diagnostic sugar. Major menaquinone was MK-9(H₆), and major fatty acids were hexadecanoic acid, 14-methylpentadecanoic acid, octadecenoic acid, and 10-methyloctadecanoic acid. Diphosphatidylglycerol, phosphatidylinositol, and phosphatidylethanolamine were detected as major phospholipid components. These morphological and chemotaxonomic features suggested that the isolates related to the genus Actinomadura, although most of Actinomadura species contain no major amount of phosphatidylethanolamine. Furthermore, comparison of the 16S rRNA genes allocates the two isolates to the genus Actinomadura. From their morphological, physiological, biochemical characteristics and DNA-DNA hybridization data, the two isolates represented two new species in the genus Actinomadura, for which we propose A. glomerata sp. nov. (type strain, I-226=JCM 9376), and A. longicatena sp. nov. (type strain, I-497=JCM 9377).

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The genus Streptomyces is characterized by its ability to produce a wide variety of secondary metabolites and complex morphological differentiation resembling that of fungi. The regulation controlling these two characteristic aspects include “eucaryotic” systems, such as a hormonal control represented by the A-factor regulatory system and protein phosphorylation represented by the afsK/afsR system. A-factor is a chemical signaling molecule that triggers both secondary metabolite formation and aerial mycelium formation in Streptomyces griseus. Characterization of the A-factor-specific receptor gene suggests that the receptor acts as a repressor-type regulator for secondary metabolite formation and morphogenesis during the early stage of growth and A-factor at a certain critical intracellular concentration releases the derepression, thus leading to the onset of secondary metabolism and aerial mycelium formation. The A-factor signal is then transferred, via one or more steps, to a transcriptional activator for the strR gene, a transcriptional activator for the whole streptomycin biosynthetic genes. Involvement of protein serine/threonine kinases in signal transduction leading to antibiotic production and morphogenesis, either as a member in the A-factor regulatory cascade or as a regulator in the pathway independent of the cascade, has also been demonstrated by the studies with afsK/afsR of Streptomyces coelicolor A3(2) and their homologs of S. griseus.

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