Bioinformatics approaches and software for detection of secondary metabolic gene clusters.
The accelerating pace of microbial genomics is sparking a renaissance in the field of natural products research. Researchers can now get a preview of the organism's secondary metabolome by analyzing its genomic sequence. Combined with other -omics data, this approach may provide a cost-effective alternative to industrial high-throughput screening in drug discovery. In the last few years, several computational tools have been developed to facilitate this process by identifying genes involved in secondary metabolite biosynthesis in bacterial and fungal genomes. Here, we review seven software programs that are available for this purpose, with an emphasis on antibiotics & Secondary Metabolite Analysis SHell (antiSMASH) and Secondary Metabolite Unknown Regions Finder (SMURF), the only tools that can comprehensively detect complete secondary metabolite biosynthesis gene clusters. We also discuss five related software packages-CLUster SEquence ANalyzer (CLUSEAN), ClustScan, Structure Based Sequence Analysis of Polyketide Synthases (SBSPKS), NRPSPredictor, and Natural Product searcher (NP.searcher)-that identify secondary metabolite backbone biosynthesis genes. This chapter offers detailed protocols, suggestions, and caveats to assist researchers in using these tools most effectively.
The J. Craig Venter Institute, Rockville, MD, USA. natalief@jcvi.org
Natalie D
ND
Fedorova
Venkatesh
V
Moktali
Marnix H
MH
Medema
D000465:Algorithms; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D001688:Biological Products / Q000378:metabolism; D019295:Computational Biology / Q000379:methods*; D005658:Fungi / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D023281:Genomics; D020407:Internet; D005810:Multigene Family / Q000235:genetics*; D048630:Polyketide Synthases / Q000235:genetics; D012984:Software
D000900:Anti-Bacterial Agents; D001688:Biological Products; D048630:Polyketide Synthases