Natural products (a.k.a. secondary metabolites) are produced by living organisms that are not essential for their growth, development, or reproduction, but may play a role in their survival or adaptability in nature. Many secondary metabolites isolated from plants and microbes have found use as molecular probes, drug leads, or medicine...
Pseudomonas fluorescens NZI7 was first isolated from a New Zealand mushroom farm in 2001. This Gram-negative bacteria can cause brown blotch disease in the basidiomycete mushroom Agaricus bisporus. P. fluorescens NZI7 can also repel grazing by the nematode Caenorhabditis elegans, a natural predator of P. fluorescens NZI7. Potentially implicated in...
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...
Sunscreen products are used worldwide to protect the skin from ultraviolet radiation. However, some of the ingredients used in sunscreen products are fatal to coral reefs especially in areas where tourism is a large part of the economy. In this study, we explored a synthetic route to produce 4-deoxygadusol, which...
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, 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...
According to the Center for Disease Control and Prevention (CDC), in 2015 10.4 million people worldwide became infected with tuberculosis (TB) with 1.8 million TB related deaths. Tuberculosis is a bacterial infectious disease caused by Mycobacterium tuberculosis, a slow growing yet highly infectious bacterium. Among the first line of treatments...
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TaifoMahmud
According to the Center for Disease Control and Prevention (CDC), in 2015
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.,...
Soil bacteria are known to be a prolific source of bioactive compounds. They
produce secondary metabolites that can be used as therapeutic agents. This investigation
focused on the chemistry and biology of secondary metabolites from two soil bacteria,
Streptomyces herbaricolor ICBB 9409 and Streptomyces albiflaviniger ICBB 9297,
which were isolated...
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...
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,...
Natural products isolated from bacteria can be developed into new therapeutic agents. The soil bacteria actinomycetes, specifically the Streptomyces species, are prolific producers of antibiotics. This thesis is composed of two projects which focus on novel drug discovery from soil bacteria collected from the Indonesian Black Water Ecosystem (the ICBB...
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...
Tuberculoѕiѕ (TB) iѕ a number one killer among treatable infectious diseases. It is caused by the pathogenic bacterium Mycobacterium tuberculoѕiѕ that primarily affects the lungѕ. It infects one third of the world population and kills approximately 2 million people each year (based on WHO report). Drug-reѕiѕtant TB haѕ become a...
The purpose of this project was to isolate gabosines and other compounds through chemical screening of secondary metabolites of Streptomyces cellulosae subsp. griseorubiginoses strain S1096. Two different media were used to cultivate S. cellulosae. The first contained soybean and mannitol. The other contained oatmeal and trace element solution. After cultivation...
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,...
Myxobacteria represent an interesting class of Gram-negative soil bacteria. These bacteria utilize organic materials from the environment as a food source by the action of their extracellular hydrolytic enzymes. They grow vegetatively in the presence of adequate nutrients. During starvation conditions, however, they aggregate and form multicellular structures called fruiting...