antiSMASH 2.0—a versatile platform for genome mining of secondary metabolite producers

Microbial secondary metabolites are a potent source of antibiotics and other pharmaceuticals. Genome mining of their biosynthetic gene clusters has become a key method to accelerate their identification and characterization. In 2011, we developed antiSMASH, a web-based analysis platform that automates this process. Here, we present the highly improved antiSMASH 2.0 release, available at http://antismash.secondarymetabolites.org/. For the new version, antiSMASH was entirely re-designed using a plug-and-play concept that allows easy integration of novel predictor or output modules. antiSMASH 2.0 now supports input of multiple related sequences simultaneously (multi-FASTA/GenBank/EMBL), which allows the analysis of draft genomes comprising multiple contigs. Moreover, direct analysis of protein sequences is now possible. antiSMASH 2.0 has also been equipped with the capacity to detect additional classes of secondary metabolites, including oligosaccharide antibiotics, phenazines, thiopeptides, homo-serine lactones, phosphonates and furans. The algorithm for predicting the core structure of the cluster end product is now also covering lantipeptides, in addition to polyketides and non-ribosomal peptides. The antiSMASH ClusterBlast functionality has been extended to identify sub-clusters involved in the biosynthesis of specific chemical building blocks. The new features currently make antiSMASH 2.0 the most comprehensive resource for identifying and analyzing novel secondary metabolite biosynthetic pathways in microorganisms.

[1]  David J Newman,et al.  Natural products as sources of new drugs over the 30 years from 1981 to 2010. , 2012, Journal of natural products.

[2]  Rainer Breitling,et al.  Computational tools for the synthetic design of biochemical pathways , 2012, Nature Reviews Microbiology.

[3]  Kyle R. Conway,et al.  ClusterMine360: a database of microbial PKS/NRPS biosynthesis , 2012, Nucleic Acids Res..

[4]  A. L. Demain,et al.  Antimicrobials, drug discovery, and genome mining , 2012, Applied Microbiology and Biotechnology.

[5]  William H. Majoros,et al.  Genomic sequence of the pathogenic and allergenic filamentous fungus Aspergillus fumigatus , 2005, Nature.

[6]  D. Haft,et al.  SMURF: Genomic mapping of fungal secondary metabolite clusters. , 2010, Fungal genetics and biology : FG & B.

[7]  Rainer Breitling,et al.  Exploiting plug-and-play synthetic biology for drug discovery and production in microorganisms , 2011, Nature Reviews Microbiology.

[8]  Jason M Crawford,et al.  Microbial genome mining answers longstanding biosynthetic questions , 2012, Proceedings of the National Academy of Sciences.

[9]  Sean R. Eddy,et al.  Accelerated Profile HMM Searches , 2011, PLoS Comput. Biol..

[10]  Carlos Prieto,et al.  NRPSsp: non-ribosomal peptide synthase substrate predictor , 2012, Bioinform..

[11]  Tilmann Weber,et al.  Specificity prediction of adenylation domains in nonribosomal peptide synthetases (NRPS) using transductive support vector machines (TSVMs) , 2005, Nucleic acids research.

[12]  Gitanjali Yadav,et al.  Towards Prediction of Metabolic Products of Polyketide Synthases: An In Silico Analysis , 2009, PLoS Comput. Biol..

[13]  Kai Blin,et al.  antiSMASH: rapid identification, annotation and analysis of secondary metabolite biosynthesis gene clusters in bacterial and fungal genome sequences , 2011, Nucleic Acids Res..

[14]  Jun Ishikawa,et al.  Genome Sequence of the Streptomycin-Producing Microorganism Streptomyces griseus IFO 13350 , 2008, Journal of bacteriology.

[15]  Gitanjali Yadav,et al.  SBSPKS: structure based sequence analysis of polyketide synthases , 2010, Nucleic Acids Res..

[16]  William Fenical,et al.  Genome sequencing reveals complex secondary metabolome in the marine actinomycete Salinispora tropica , 2007, Proceedings of the National Academy of Sciences.

[17]  Jacques Ravel,et al.  Chapter 8. Methods for in silico prediction of microbial polyketide and nonribosomal peptide biosynthetic pathways from DNA sequence data. , 2009, Methods in enzymology.

[18]  J. Recktenwald,et al.  Identification and Analysis of the Balhimycin Biosynthetic Gene Cluster and Its Use for Manipulating Glycopeptide Biosynthesis in Amycolatopsis mediterranei DSM5908 , 1999, Antimicrobial Agents and Chemotherapy.

[19]  Gregory Kucherov,et al.  NORINE: a database of nonribosomal peptides , 2007, Nucleic Acids Res..

[20]  E. Birney,et al.  Pfam: the protein families database , 2013, Nucleic Acids Res..

[21]  Marnix H Medema,et al.  Bioinformatics approaches and software for detection of secondary metabolic gene clusters. , 2012, Methods in molecular biology.

[22]  Rekha Seshadri,et al.  Complete genome sequence of the plant commensal Pseudomonas fluorescens Pf-5 , 2005, Nature Biotechnology.

[23]  R. Breitling,et al.  Detecting Sequence Homology at the Gene Cluster Level with MultiGeneBlast , 2013, Molecular biology and evolution.

[24]  Leonard Katz,et al.  Genome-based bioprospecting of microbes for new therapeutics. , 2012, Current opinion in biotechnology.

[25]  Oscar P. Kuipers,et al.  BAGEL2: mining for bacteriocins in genomic data , 2010, Nucleic Acids Res..

[26]  Kai Blin,et al.  NRPSpredictor2—a web server for predicting NRPS adenylation domain specificity , 2011, Nucleic Acids Res..

[27]  I. Hoof,et al.  CLUSEAN: a computer-based framework for the automated analysis of bacterial secondary metabolite biosynthetic gene clusters. , 2009, Journal of biotechnology.

[28]  Minoru Kanehisa,et al.  Comprehensive analysis of distinctive polyketide and nonribosomal peptide structural motifs encoded in microbial genomes. , 2007, Journal of molecular biology.

[29]  J. Zucko,et al.  ClustScan: an integrated program package for the semi-automatic annotation of modular biosynthetic gene clusters and in silico prediction of novel chemical structures , 2008, Nucleic acids research.

[30]  H. Ikeda,et al.  Genome Sequence of Kitasatospora setae NBRC 14216T: An Evolutionary Snapshot of the Family Streptomycetaceae , 2010, DNA research : an international journal for rapid publication of reports on genes and genomes.

[31]  Tilmann Weber,et al.  In silico tools for the analysis of antibiotic biosynthetic pathways. , 2014, International journal of medical microbiology : IJMM.