Microbial secondary metabolism constitutes a rich source of antibiotics, chemotherapeutics, insecticides and other high-value chemicals. Genome mining of gene clusters that encode the biosynthetic pathways for these metabolites has become a key methodology for novel compound discovery. In 2011, we introduced antiSMASH, a web server and stand-alone tool for the automatic genomic identification and analysis of biosynthetic gene clusters, available at http://antismash.secondarymetabolites.org. Here, we present version 3.0 of antiSMASH, which has undergone major improvements. A full integration of the recently published ClusterFinder algorithm now allows using this probabilistic algorithm to detect putative gene clusters of unknown types. Also, a new dereplication variant of the ClusterBlast module now identifies similarities of identified clusters to any of 1172 clusters with known end products. At the enzyme level, active sites of key biosynthetic enzymes are now pinpointed through a curated pattern-matching procedure and Enzyme Commission numbers are assigned to functionally classify all enzyme-coding genes. Additionally, chemical structure prediction has been improved by incorporating polyketide reduction states. Finally, in order for users to be able to organize and analyze multiple antiSMASH outputs in a private setting, a new XML output module allows offline editing of antiSMASH annotations within the Geneious software.

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Some bacterial clades are important sources of novel bioactive natural products. Estimating the magnitude of chemical diversity available from such a resource is complicated by issues including cultivability, isolation bias and limited analytical data sets. Here we perform a systematic metabolite survey of ~2300 bacterial strains of the order Myxococcales, a well-established source of natural products, using mass spectrometry. Our analysis encompasses both known and previously unidentified metabolites detected under laboratory cultivation conditions, thereby enabling large-scale comparison of production profiles in relation to myxobacterial taxonomy. We find a correlation between taxonomic distance and the production of distinct secondary metabolite families, further supporting the idea that the chances of discovering novel metabolites are greater by examining strains from new genera rather than additional representatives within the same genus. In addition, we report the discovery and structure elucidation of rowithocin, a myxobacterial secondary metabolite featuring an uncommon phosphorylated polyketide scaffold.

Diabetes is a metabolic disorder that has emerged recently as a major cause of global concern. Regulation of the blood glucose concentration is essential to maintain the homeostasis. GLUT2, a carrier protein, plays an important role in transporting sugar molecules across the membrane. To understand the function of this carrier molecule, knowledge of its three-dimensional structure is of paramount importance. Homology modeling approach was adopted to decipher the threedimensional structure and features of human GLUT2. Ninety-eight percent residues of the modeled structure lie in the allowed region of the Ramachandran plot and a RMSD of 0.86 Å with the template molecule confirms the reliability of the modeled structure. Comparative transmembrane helix prediction from primary sequence as well as analysis of model revealed presence of 12 helices, which is in agreement with the available literature. Molecular mechanical calculations and docking analysis were performed for the selected 33 compounds. Results showed Glipizide as the best interacting ligand based on the fitness values scored from the binding affinity and minimized energy of the docked complex. These results will aid in efficient designing of inhibitor molecules to curb diabetes.

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