The metabolites of the manumycin family are known to have a broad range of antibiotic functions including antibacterial, anticoccidial, and antifungal activities (1). Manumycin compounds also display a strong activity against farnesyltransferase, IB kinase , interleukin-1-converting enzymes, and acetylcholinesterase and are considered as drug candidates to treat cancers, inflammation, and Alzheimer disease (1-4). Asukamycin A1, a manumycin-type metabolite, contains a unique 2-amino-4-hydroxy-5,6-epoxycyclohex-2-enone (mC 7 N) 3 core and two trans-triene polyketide chains, in which the upper one starts with a cyclohexane ring, and the lower one terminates in the five-membered ring of a 2-amino-3-hydroxycyclopent-2-enone (C 5 N) moiety (Fig.
Spore awakening is a series of actions that starts with purely physical processes and continues via the launching of gene expression and metabolic activities, eventually achieving a vegetative phase of growth. In spore-forming microorganisms, the germination process is controlled by intra- and inter-species communication. However, in the Streptomyces clade, which is capable of developing a plethora of valuable compounds, the chemical signals produced during germination have not been systematically studied before. Our previously published data revealed that several secondary metabolite biosynthetic genes are expressed during germination. Therefore, we focus here on the secondary metabolite production during this developmental stage. Using high-performance liquid chromatography-mass spectrometry, we found that the sesquiterpenoid antibiotic albaflavenone, the polyketide germicidin A, and chalcone are produced during germination of the model streptomycete, S. coelicolor. Interestingly, the last two compounds revealed an inhibitory effect on the germination process. The secondary metabolites originating from the early stage of microbial growth may coordinate the development of the producer (quorum sensing) and/or play a role in competitive microflora repression (quorum quenching) in their nature environments.
The increasing number of genes encoding eukaryotic-type Ser/Thr protein kinases (ESTPKs) in prokaryotes, identified mostly due to genome-sequencing projects, suggests that these enzymes play an indispensable role in many bacterial species. Some prokaryotes, such as Streptomyces coelicolor, carry numerous genes of this type. Though the regulatory pathways have been intensively studied in the organism, experimental proof of the physiological function of ESTPKs is scarce. This review presents a family portrait of the genes identified in the sequence of the S. coelicolor A3(2) genome. Based on the available experimental data on ESTPKs in streptomycetes and related bacteria, and on computer-assisted sequence analyses, possible roles of these enzymes in the regulation of cellular processes in streptomycetes are suggested.
Streptomycetes, typical soil dwellers, can be detected as common colonizers of human bodies, especially the skin, the respiratory tract, the guts and the genital tract using molecular techniques. However, their clinical manifestations and isolations are rare. Recently they were discussed as possible "coaches" of the human immune system in connection with certain immune disorders and cancer. This work aimed for the characterization and evaluation of genetic adaptations of a human-associated strain Streptomyces sp. TR1341. The strain was isolated from sputum of a senior male patient with a history of lung and kidney TB, recurrent respiratory infections and COPD. It manifested remarkably broad biological activities (antibacterial, antifungal, betahemolytic, etc.). We found that, by producing specific secondary metabolites, it is able to modulate host immune responses and the niche itself, which increase its chances for long-term survival in the human tissue. The work shows possible adaptations or predispositions of formerly soil microorganism to survive in human tissue successfully. The strain produces two structural groups of cytotoxic compounds: 28-carbon cytolytic polyenes of the filipin type and actinomycin X2. Additionally, we summarize and present data about streptomycete-related human infections known so far.
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