Ribomimetic natural products have long been known for their important biological activities. Structurally, they contain a densely functionalized cyclopentane unit that resembles ribose. Pactamycin, the prominent member of this class of natural products, is a potent protein synthesis inhibitor produced by the soil bacterium Streptomyces pactum. In pactamycin, the aminocyclopentitol...
Among the myriad of natural products are pseudosugar-containing secondary metabolites, e.g., the C7-pseudosugar-containing oligosaccharide acarbose, the C6- pseudosugar-containing aminoglycoside antibiotics, and the five-membered ring pseudosugar-containing antibiotic pactamycin. The C7-pseudosugars are normally derived from sedoheptulose 7-phosphate catalyzed by a family of enzymes called sedoheptulose 7-phosphate cyclases (SH7PCs). This family of enzymes...
Pactamycin, a potent antitumor antibiotic produced by the soil bacterium Streptomycespactum, is a structurally unique aminocyclopentitol-containing natural product. Itconsists of a highly functionalized cyclopentitol core unit, two aromatic rings [3-aminoacetophenone (3AAP) and 6-methylsalicylic acid (6MSA)], and a 1,1-dimethylurea moiety. Despite its potent biological activity, the development of thisantibiotic was hampered...
Among the myriad of naturally occurring bioactive compounds are the aminocyclopentitol-containing natural products that represent a family of sugar-derived microbial secondary metabolites, such as the antibiotics pactamycin, allosamidin, and trehazolin. Pactamycin, a structurally unique aminocyclitol antibiotic isolated from Streptomyces pactum, consists of a 5-membered ring aminocyclitol (cyclopentitol) unit, two aromatic...
Asukamycin, a member of the manumycin family of antibiotics, exhibits strong antibacterial, antifungal, and anti-neoplastic activities. However, its production in the wild-type strain of Streptomyces nodosus subsp. asukaensis ATCC 29757 is relatively low. Recently, the biosynthetic gene cluster for asukamycin was identified in the producing organism and among the 36...
The prevalence of obesity and diabetes in the United States and globally has been rising in the last few decades and it continues to climb. One of the causes for this increase is the over consumption of sugars and/or carbohydrates. Among medications available to treat obesity and diabetes are the...
Pactamycin, a complex aminocyclitol compound produced by Streptomyces pactum, has significant antibiotic, antitumor, and antiplasmodial activity. However, this natural product has not been developed for clinical use due to its high cytotoxicity. Modulation of its biological properties by chemical synthesis has been difficult due to its complex chemical structure. Therefore,...
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Research Thesis Seminar Presentation
Streptomycespactum produces the antitumor
antibiotic pactamycin
Pactamycin, a complex aminocyclitol compound produced by Streptomyces pactum, has significant antibiotic, antitumor, and antiplasmodial activity. However, this natural product has not been developed for clinical use due to its high cytotoxicity. Modulation of its biological properties by chemical synthesis has been difficult due to its complex chemical structure. Therefore,...
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Abstract
Pactamycin, a complex aminocyclitol compound produced by Streptomycespactum, has
significant
Pactamycin, produced by the soil bacterium Streptomyces pactum, is a cytotoxic antibiotic that belongs to the aminocyclitol family of natural products. This antibiotic has shown various forms of biological activity, including antibacterial, antifungal, antimalarial, and antitumor activities. Despite its outstanding biological activity, the mode of formation of its pharmacophore (the...
Pactamycin, a complex aminocyclitol compound produced by Streptomyces pactum, has significant antibiotic, antitumor, and antiplasmodial activity. However, this natural product has not been developed for clinical use due to its high cytotoxicity. Modulation of its biological properties by chemical synthesis has been difficult due to its complex chemical structure. Therefore,...
Pactamycin, first reported in 1962, is a potent antitumor antibiotic produced by the soil bacterium Streptomyces pactum. Structurally, it contains a cyclopentitol core unit, a 3-aminoacetophenone (3AAP), a 6-methylsalicylic acid (6-MSA), and a N,N-dimethyl urea. The aminocyclopentitol ring is derived from glucose, possibly via N-acetyl glucosamine (GlcNAc), the 3-aminoacetophenone (3AAP)...
Despite the advance of biomedical science, infectious diseases remain one of the number one killers in the world. They claim the lives of millions of people annually, particularly in underdeveloped and developing countries. In fact, more than 32% of the health burden in Africa is caused by infectious diseases, e.g.,...
Sugar phosphate cyclases (SPCs) are enzymes involved in the biosynthesis of many important natural products. SPCs form a unique cyclitol during the early steps in the biosynthesis of many natural products. These natural products include rifamycin, which is chemically modified to rifampicin and used clinically as an antituberculosis drug, and...
Pactamycin, although putatively touted as a potent antitumor agent, has never been used as an anticancer drug due to its high cytotoxicity. In this study, we characterized the effects of two novel biosynthetically engineered analogs of pactamycin, de-6MSA-7-demethyl-7- deoxypactamycin (TM-025) and 7-demethyl-7-deoxypactamycin (TM-026), in head and neck squamous cell carcinoma...