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antiSMASH 3.0—a comprehensive resource for the genome mining of biosynthetic gene clusters
Weber, Tilmann,Blin, Kai,Duddela, Srikanth,Krug, Daniel,Kim, Hyun Uk,Bruccoleri, Robert,Lee, Sang Yup,Fischbach, Michael A,Mü,ller, Rolf,Wohlleben, Wolfgang,Breitling, Rainer,Takano, Eriko,Medema, Oxford University Press 2015 Nucleic acids research Vol.43 No.w1
<P><B>Abstract</B></P><P>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.</P>
Antonia Richter,Karina Knorr,Martin Schlapschy,Stephanie Robu,Volker Morath,Claudia Mendler,Hsi-Yu Yen,Katja Steiger,Marion Kiechle,Wolfgang Weber,Arne Skerra,Markus Schwaiger 대한핵의학회 2020 핵의학 분자영상 Vol.54 No.2
Purpose PASylation® offers the ability to systematically tune and optimize the pharmacokinetics of protein tracers for molecular imaging. Here we report the first clinical translation of a PASylated Fab fragment (89Zr∙Df-HER2-Fab-PAS200) for the molecular imaging of tumor-related HER2 expression. Methods A patient with HER2-positive metastatic breast cancer received 37 MBq of 89Zr∙Df-HER2-Fab-PAS200 at a total mass dose of 70 μg. PET/CT was carried out 6, 24, and 45 h after injection, followed by image analysis of biodistribution, normal organ uptake, and lesion targeting. Results Images show a biodistribution typical for protein tracers, characterized by a prominent blood pool 6 h p.i., which decreased over time. Lesions were detectable as early as 24 h p.i. 89Zr∙Df-HER2-Fab-PAS200 was tolerated well. Conclusion This study demonstrates that a PASylated Fab tracer shows appropriate blood clearance to allow sensitive visualization of small tumor lesions in a clinical setting.