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...
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, 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)...
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...
The discovery of new antibiotics reached its peak during the golden era of antibiotics in the mid 20th century and continued to thrive until the 1980s. However, after more than 50 years of fruitful exploration and exploitation of microbial natural products the discovery rate of new antibiotics has dropped drastically...
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.,...
This thesis describes an investigation of the molecular basis of the substrate specificity and catalytic mechanism of a unique pseudoglycosyltransferase (PsGT) enzyme, VldE. PsGTs are a newly discovered group of glycosyltransferase (GT)-like proteins that catalyze the transfer of a pseudosugar to an acceptor molecule via a C-N bond formation. This...
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...
A gene cluster responsible for the biosynthesis of the antitumor agent
cetoniacytone A was identified in Actinomyces sp. strain Lu 9419, an
endosymbiotic bacteria isolated from the intestines of the rose chafer beetle. The
nucleotide sequence analysis of the 26 Kb DNA region revealed the presence of 17
complete ORFs,...