Recent figures indicate that the global incidence of several types of fungal diseases have been under-documented, among which mortality caused by invasive fungal infections remains disturbingly high. And thus, it is obvious that discovery of novel antifungal drugs is quite necessary and promising. Creative Biolabs is a world top CRO focused on drug discovery, with decades of experience in discovering potential targets for antifungal drug discovery. Now, a group of senior scientists are ready to provide target identification services, especially for sulfate assimilation (SA) pathway.
Sulfate Assimilation (SA) Pathway
Fungi are characterized by their metabolic versatility, whether it is the degradation of complex organic substrates or the biosynthesis of intricate secondary metabolites. Sulfur is a fundamental nutrient for fungus since it plays essential roles in many metabolic processes. It is found in the amino acids cysteine and methionine, which are commonly responsible for the structure and biological activity of proteins, and also in other essential organic molecules, such as iron-sulfur (Fe-S) clusters, coenzyme-A, glutathione,etc. The sulfate assimilation (SA) pathway has been well-defined, which comprises the uptake of sulfate by specialized permeases, activation by ATP-driven phosphorylation in two steps, and reduction to sulfite and further to sulfide.
The SA pathway is responsible for the cysteine biosynthesis and involves high and low affinity sulfate transporters, and the enzymes such as ATP sulfurylase, APS kinase, PAPS reductase or APS reductase, serine acetyl transferase, sulfite reductase, O-acetylserine/O-acetylhomoserine sulfhydrylase and, also cystathionine b-synthase and cystathionine c-lyase in some organisms. Oxidative stress, sulfur deficiency, and heavy metal exposure are shown to affect the biochemical and genetic regulation of the SA pathway.
Fig.1 Scheme of sulfate assimilation. (Koprivova, 2014)
Sulfate Assimilation (SA) Pathway as a Target for Antifungal Drug Discovery
Nutrient supply is an essential precondition for the onset and manifestation of infection by any pathogen. The growth and nutritional requirements of fungi during infection are supposed to be relevant for the invasion of the host. The acquisition of nutrients by the invading microorganism is required by the proliferation at the intimate host-pathogen interface. Since sulfate is an essential nutrient for fungus, elucidating the SA pathway is a prerequisite for deducing general principles of pathogenesis for related infectious diseases and identifying potential antifungal therapeutic targets.
Microbial metabolism is critical for pathogenesis, and several biosynthetic pathways have already been established to represent valid targets for chemotherapeutic intervention. And previous studies have suggested that proper regulation of the SA pathway is essential for A. fumigatus virulence. As always focused on the research spotlight of drug discovery, Creative Biolabs is now ready to assist you in identifying the sulfate assimilation pathway as a novel target for antifungal drug discovery.
Why Choose Us?
To meet the challenging requirements, Creative Biolabs has built a team of experienced scientists with facilities and processes designed specifically to provide the best strategy and protocols customized to suit any antifungal drug discovery projects. We can provide various identification services for Fungal Nucleic Acid and Protein Biosynthesis Targets, including:
In addition to the identification of potential targets for antifungal drug discovery, you might be also interested in other services for Potential Targets for Antifungal Drug Discovery listed below:
If you have any special needs in discovering potential targets for antifungal drugs or be interested in learning more about our antifungal drug discovery services, please feel free to contact us for more details.
Reference
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