Cyanobacteria are considered a promising source for new ‎pharmaceutical lead compounds and a large number of chemically diverse and ‎bioactive metabolites have been obtained from cyanobacteria. Despite of ‎several worldwide studies on prevalence of NRPSs and PKSs among the ‎cyanobacteria, none of them included Iranian cyanobacteria of Kermanshah ‎province. Therefore, the aim of this study was t...

Nonribosomal peptide synthetases (NRPSs) are large, multidomain proteins that are involved in the biosynthesis of an array of secondary metabolites. We report the structure of the third adenylation domain from the siderophore-synthesizing NRPS, SidN, from the endophytic fungus Neotyphodium lolii. This is the first structure of a eukaryotic NRPS domain, and it reveals a large binding pocket requ...

The Hedgehog (Hh) pathway is essential for vertebrate embryogenesis, and excessive Hh target gene activation can cause cancer in humans. Here we show that Neuropilin 1 (Nrp1) and Nrp2, transmembrane proteins with roles in axon guidance and vascular endothelial growth factor (VEGF) signaling, are important positive regulators of Hh signal transduction. Nrps are expressed at times and locations o...

Recent investigations highlighted strong similarities between neural crest migration during embryogenesis and metastatic processes. Indeed, some families of axon guidance molecules were also reported to participate in cancer invasion: plexins/semaphorins/neuropilins, ephrins/Eph receptors, netrin/DCC/UNC5. Neuropilins (NRPs) are transmembrane non tyrosine-kinase glycoproteins first identified a...

Leinamycin (LNM), produced by Streptomyces atroolivaceus, is a thiazole-containing hybrid peptide-polyketide natural product structurally characterized with an unprecedented 1,3-dioxo-1,2-dithiolane moiety that is spiro-fused to a 18-member macrolactam ring. LNM exhibits a broad spectrum of antimicrobial and antitumor activities, most significantly against tumors that are resistant to clinicall...

Analyses of microbial genome sequences reveal numerous examples of gene clusters encoding proteins typically involved in complex natural product biosynthesis but not associated with the production of known natural products1–3. In Streptomyces coelicolor M145 there are several gene clusters encoding new nonribosomal peptide synthetase (NRPS) systems not associated with known metabolites. Applica...

Aryl-aldehydes are a common feature in fungal polyketides, which are considered to be exclusively generated by the R domain of nonreducing polyketide synthases (NR-PKSs). However, by cloning and heterologous expression of both cryptic NR-PKS and nonribosomal peptide synthase (NRPS)-like genes from Aspergillus terreus in Saccharomyces cerevisiae, we identified a distinct mechanism for aryl-aldeh...

New insight in the ochratoxin A biosynthetic pathway by deletion of an nrps 1 gene in Aspergillus carbonarius 2 3 Antonia Gallo, Kenneth S. Bruno, Michele Solfrizzo, Giancarlo Perrone, Giuseppina 4 Mulè, Angelo Visconti and Scott E. Baker 5 6 Institute of Sciences of Food Production (ISPA), National Research Council (CNR), Bari, Italy. 7 8 Chemical and Biological Process Development Group, Paci...

VEGFs (vascular endothelial growth factors) are master regulators of vascular development and of blood and lymphatic vessel function during health and disease in adults. This family of five mammalian ligands acts through three RTKs (receptor tyrosine kinases). In addition, co-receptors such as NRPs (neuropilins) associate with the ligand-receptor signalling complex and modulate the output. Ther...