As a leading company in preclinical drug discovery, Creative Biolabs has gained a wealth of experience in the development of antifungal drug discovery. We perform advanced technology-based assays to exploit potential antifungal targets for the treatment of numerous fungal infections. Now, we are happy to introduce our target discovery services against phosphopantetheinyl transferases.
Introduction of Phosphopantetheinyl Transferases
Phosphopantetheinyl transferases, also known as PPTases, are found in bacterial, fungal, and mammalian cells. They are essential for cell viability across all three domains of life: bacteria, archaea, and eukaryota. Studies have shown that PPTases play an important enzymatic role in general fatty acid biosynthesis as well as a wide diversity of secondary metabolism. In fungal genomes, there are three types of PPTase. The first is integrated within the cytoplasmic fatty acid synthase and transfers the 4’PPT group to an acyl carrier protein (ACP) domain within the same protein. The second (Lys5 in Saccharomyces cerevisiae and C. albicans; PptA in A. fumigatus) is involved in lysine biosynthesis, activating α-aminoadipate reductase with further functions including activation of PKS and NRPS. The third PPTase, (Ppt2 in S. cerevisiae; PptB in A. fumigatus) is involved in the mitochondrial fatty acid synthesis, and is required to transfer the 4’PPT from CoA to the mitochondrial acyl carrier protein Acp1.
Fig.1 Schematic diagram of the role played by AcpS and PptT in the fatty acid, mycolic acid, methyl-branched-containing lipid, and siderophore biosynthesis pathways in M. tuberculosis. (Chalut,2006)
Phosphopantetheinyl Transferases as Potential Antifungal Target
Based on primary structure and their key metabolic positions in metabolism, PPTases are grouped into two classes: the AcpS-type and Sfp-type PPTases. The AcpS-type is typically associated with fatty acid biosynthesis, Sfp-type PPTases, corresponding to the activator of surfactin production in Bacillus subtilis, are generally responsible for modifying type I polyketide and nonribosomal peptide synthases of prokaryotes. Particularly, the essential nature of PPTases to primary metabolism makes them enticing targets for antibiotic development. Additionally, Sfp-type PPTases are responsible for activating biosynthetic pathways that manufacture a variety of pathogen-associated virulence factors. Furthermore, recent studies indicated that PPTases in A. fumigatus and C. albicans are essential for their viability. Thus, PPTases have been proposed as potential antifungal targets.
During the past years, we have successfully established a state-of-the-art platform for antifungal drug discovery. We are able to offer numerous target identification and validation services for potential target exploiting. Except for phosphopantetheinyl transferases, we also offer other potential cellular function-related targets exploiting service for antifungal drug discovery, which including but not limited to:
Creative Biolabs is confident in providing high-quality target exploiting services for the development of antifungal drug discovery. For more detailed information, please feel free to contact us.
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