Computational approaches to natural product discovery.
Starting with the earliest Streptomyces genome sequences, the promise of natural product genome mining has been captivating: genomics and bioinformatics would transform compound discovery from an ad hoc pursuit to a high-throughput endeavor. Until recently, however, genome mining has advanced natural product discovery only modestly. Here, we argue that the development of algorithms to mine the continuously increasing amounts of (meta)genomic data will enable the promise of genome mining to be realized. We review computational strategies that have been developed to identify biosynthetic gene clusters in genome sequences and predict the chemical structures of their products. We then discuss networking strategies that can systematize large volumes of genetic and chemical data and connect genomic information to metabolomic and phenotypic data. Finally, we provide a vision of what natural product discovery might look like in the future, specifically considering longstanding questions in microbial ecology regarding the roles of metabolites in interspecies interactions.
Bioinformatics Group, Wageningen University, Wageningen, the Netherlands.
Marnix H
MH
Medema
1] Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, California, USA. [2] California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, California, USA.
Michael A
MA
Fischbach
D000465:Algorithms; D000470:Alkaloids / Q000096:biosynthesis; D001419:Bacteria / Q000235:genetics* / Q000378:metabolism; D001688:Biological Products / Q000737:chemistry / Q000378:metabolism*; D019295:Computational Biology / Q000295:instrumentation / Q000379:methods*; D057225:Data Mining; D030541:Databases, Genetic; D005658:Fungi / Q000235:genetics* / Q000378:metabolism; D054892:Metagenome; D005810:Multigene Family; D046908:Peptide Biosynthesis, Nucleic Acid-Independent; D010455:Peptides / Q000378:metabolism; D010944:Plants / Q000235:genetics* / Q000378:metabolism; D061065:Polyketides / Q000378:metabolism; D011134:Polysaccharides / Q000096:biosynthesis; D013729:Terpenes / Q000378:metabolism
D000470:Alkaloids; D001688:Biological Products; D010455:Peptides; D061065:Polyketides; D011134:Polysaccharides; D013729:Terpenes