Guadinomines are anti-infective compounds produced by Streptomyces sp. K01-0509. [1] Guadinomine B is the most potent known inhibitor of the Type III secretion system (TTSS) of Gram-negative bacteria. The guadinomine (gdn) biosynthetic gene cluster includes 26 open reading frames spanning 51.2 kb. Streptomyces sp. K01-0509 produces several derivatives named guadinomines A, B, C1, C2, D, and guadinomic acid. [2]
The Actinomycetota are a phylum of mostly Gram-positive bacteria. They can be terrestrial or aquatic. They are of great economic importance to humans because agriculture and forests depend on their contributions to soil systems. In soil they help to decompose the organic matter of dead organisms so the molecules can be taken up anew by plants. While this role is also played by fungi, Actinomycetota are much smaller and likely do not occupy the same ecological niche. In this role the colonies often grow extensive mycelia, like a fungus would, and the name of an important order of the phylum, Actinomycetales, reflects that they were long believed to be fungi. Some soil actinomycetota live symbiotically with the plants whose roots pervade the soil, fixing nitrogen for the plants in exchange for access to some of the plant's saccharides. Other species, such as many members of the genus Mycobacterium, are important pathogens.
Streptomyces is the largest genus of Actinomycetota and the type genus of the family Streptomycetaceae. Over 500 species of Streptomyces bacteria have been described. As with the other Actinomycetota, streptomycetes are gram-positive, and have genomes with high GC content. Found predominantly in soil and decaying vegetation, most streptomycetes produce spores, and are noted for their distinct "earthy" odor that results from production of a volatile metabolite, geosmin.
Novobiocin, also known as albamycin or cathomycin, is an aminocoumarin antibiotic that is produced by the actinomycete Streptomyces niveus, which has recently been identified as a subjective synonym for S. spheroides a member of the class Actinomycetia. Other aminocoumarin antibiotics include clorobiocin and coumermycin A1. Novobiocin was first reported in the mid-1950s.
Streptomyces clavuligerus is a species of Gram-positive bacterium notable for producing clavulanic acid.
Glucagon-like peptide-1 (GLP-1) is a 30- or 31-amino-acid-long peptide hormone deriving from the tissue-specific posttranslational processing of the proglucagon peptide. It is produced and secreted by intestinal enteroendocrine L-cells and certain neurons within the nucleus of the solitary tract in the brainstem upon food consumption. The initial product GLP-1 (1–37) is susceptible to amidation and proteolytic cleavage, which gives rise to the two truncated and equipotent biologically active forms, GLP-1 (7–36) amide and GLP-1 (7–37). Active GLP-1 protein secondary structure includes two α-helices from amino acid position 13–20 and 24–35 separated by a linker region.
The avermectins are a series of drugs and pesticides used to treat parasitic worms and insect pests. They are a group of 16-membered macrocyclic lactone derivatives with potent anthelmintic and insecticidal properties. These naturally occurring compounds are generated as fermentation products by Streptomyces avermitilis, a soil actinomycete. Eight different avermectins were isolated in four pairs of homologue compounds, with a major (a-component) and minor (b-component) component usually in ratios of 80:20 to 90:10. Other anthelmintics derived from the avermectins include ivermectin, selamectin, doramectin, eprinomectin, and abamectin.
Collectins (collagen-containing C-type lectins) are a part of the innate immune system. They form a family of collagenous Ca2+-dependent defense lectins, which are found in animals. Collectins are soluble pattern recognition receptors (PRRs). Their function is to bind to oligosaccharide structure or lipids that are on the surface of microorganisms. Like other PRRs they bind pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs) of oligosaccharide origin. Binding of collectins to microorganisms may trigger elimination of microorganisms by aggregation, complement activation, opsonization, activation of phagocytosis, or inhibition of microbial growth. Other functions of collectins are modulation of inflammatory, allergic responses, adaptive immune system and clearance of apoptotic cells.
Staurosporine is a natural product originally isolated in 1977 from the bacterium Streptomyces staurosporeus. It was the first of over 50 alkaloids to be isolated with this type of bis-indole chemical structure. The chemical structure of staurosporine was elucidated by X-ray analysis of a single crystal and the absolute stereochemical configuration by the same method in 1994.
Type three secretion system is a protein appendage found in several Gram-negative bacteria.
Renin inhibitors are pharmaceutical drugs inhibiting the activity of renin that is responsible for hydrolyzing angiotensinogen to angiotensin I, which in turn reduces the formation of angiotensin II that facilitates blood pressure.
Indolocarbazoles (ICZs) are a class of compounds that are under current study due to their potential as anti-cancer drugs and the prospective number of derivatives and uses found from the basic backbone alone. First isolated in 1977, a wide range of structures and derivatives have been found or developed throughout the world. Due to the extensive number of structures available, this review will focus on the more important groups here while covering their occurrence, biological activity, biosynthesis, and laboratory synthesis.
Streptomyces avermitilis is a species of bacteria in the genus Streptomyces. This bacterium was discovered by Satoshi Ōmura in Shizuoka Prefecture, Japan.
Germicidins are a groups of natural products arising from Streptomyces species that acts as autoregulatory inhibitor of spore germination. In Streptomyces viriochromogenes, low concentrations inhibit germination of its own arthrospores, and higher concentrations inhibit porcine Na+/K+ -activated ATPase. Inhibitory effects on germination are also observed when germicidin from Streptomyces is applied to Lepidium sativum. Germicidins and other natural products present potential use as pharmaceuticals, and in this case, those with possible antibiotic or antifungal activity.
Bacterial effectors are proteins secreted by pathogenic bacteria into the cells of their host, usually using a type 3 secretion system (TTSS/T3SS), a type 4 secretion system (TFSS/T4SS) or a Type VI secretion system (T6SS). Some bacteria inject only a few effectors into their host’s cells while others may inject dozens or even hundreds. Effector proteins may have many different activities, but usually help the pathogen to invade host tissue, suppress its immune system, or otherwise help the pathogen to survive. Effector proteins are usually critical for virulence. For instance, in the causative agent of plague, the loss of the T3SS is sufficient to render the bacteria completely avirulent, even when they are directly introduced into the bloodstream. Gram negative microbes are also suspected to deploy bacterial outer membrane vesicles to translocate effector proteins and virulence factors via a membrane vesicle trafficking secretory pathway, in order to modify their environment or attack/invade target cells, for example, at the host-pathogen interface.
Streptomyces isolates have yielded the majority of human, animal, and agricultural antibiotics, as well as a number of fundamental chemotherapy medicines. Streptomyces is the largest antibiotic-producing genus of Actinomycetota, producing chemotherapy, antibacterial, antifungal, antiparasitic drugs, and immunosuppressants. Streptomyces isolates are typically initiated with the aerial hyphal formation from the mycelium.
Penicillium pinophilum is a species of fungus in the genus Penicillium which was isolated from a radio set in Papua New Guinea. Penicillium pinophilum produces 3-O-methylfunicone and mycophenolic acid
Satoshi Ōmura is a Japanese biochemist. He is known for the discovery and development of hundreds of pharmaceuticals originally occurring in microorganisms. In 2015, he was awarded the Nobel Prize in Physiology or Medicine jointly with William C. Campbell for their role in the discovery of avermectins and ivermectin, the world's first endectocide and a safe and highly effective microfilaricide. It is believed that the large molecular size of ivermectin prevents it from crossing the blood/aqueous humour barrier, and renders the drug an important treatment of helminthically-derived blindness.
Streptomyces halstedii is a bacterium species from the genus of Streptomyces which has been isolated from deeper soil layers. Streptomyces halstedii produces magnamycin B, vicenistatin deltamycin A2, deltamycin A3, bafilomycin B1 and bafilomycin C1. Streptomyces halstedii also produces complex antifungal antibiotics like oligomycins and the antibiotics anisomycin and sinefungin.
Embleya scabrispora is a bacterium species from the genus Embleya which has been isolated from soil from Japan. Embleya scabrispora produces the antibiotic hitachimycin.
Bacterial secretion systems are protein complexes present on the cell membranes of bacteria for secretion of substances. Specifically, they are the cellular devices used by pathogenic bacteria to secrete their virulence factors to invade the host cells. They can be classified into different types based on their specific structure, composition and activity. Generally, proteins can be secreted through two different processes. One process is a one-step mechanism in which proteins from the cytoplasm of bacteria are transported and delivered directly through the cell membrane into the host cell. Another involves a two-step activity in which the proteins are first transported out of the inner cell membrane, then deposited in the periplasm, and finally through the outer cell membrane into the host cell.
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