Elucidating the Rimosamide-Detoxin Natural Product Families and Their Biosynthesis Using Metabolite/Gene Cluster Correlations.
As microbial genome sequencing becomes more widespread, the capacity of microorganisms to produce an immense number of metabolites has come into better view. Utilizing a metabolite/gene cluster correlation platform, the biosynthetic origins of a new family of natural products, the rimosamides, were discovered. The rimosamides were identified in Streptomyces rimosus and associated with their NRPS/PKS-type gene cluster based upon their high frequency of co-occurrence across 179 strains of actinobacteria. This also led to the discovery of the related detoxin gene cluster. The core of each of these families of natural products contains a depsipeptide bond at the point of bifurcation in their unusual branched structures, the origins of which are definitively assigned to nonlinear biosynthetic pathways via heterologous expression in Streptomyces lividans. The rimosamides were found to antagonize the antibiotic activity of blasticidin S against Bacillus cereus.
Department of Chemistry, Northwestern University , Evanston, Illinois 60208, United States.
Ryan A
0000-0002-0163-9290
RA
McClure
Department of Chemistry, Northwestern University , Evanston, Illinois 60208, United States.
Anthony W
AW
Goering
Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign , Urbana, Illinois 61801, United States.
Kou-San
KS
Ju
Boyce Thompson Institute and Department of Chemistry and Chemical Biology, Cornell University , Ithaca, New York 14853, United States.
Joshua A
JA
Baccile
Boyce Thompson Institute and Department of Chemistry and Chemical Biology, Cornell University , Ithaca, New York 14853, United States.
Frank C
FC
Schroeder
Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign , Urbana, Illinois 61801, United States.|Department of Microbiology, University of Illinois at Urbana-Champaign , Urbana, Illinois 61801, United States.
William W
WW
Metcalf
Department of Chemistry, Northwestern University , Evanston, Illinois 60208, United States.
Regan J
RJ
Thomson
Department of Chemistry, Northwestern University , Evanston, Illinois 60208, United States.
Neil L
0000-0002-8815-3372
NL
Kelleher
D001688:Biological Products / Q000737:chemistry / Q000378:metabolism*; D053898:Biosynthetic Pathways; D004151:Dipeptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005798:Genes, Bacterial; D055432:Metabolomics; D005810:Multigene Family; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011759:Pyrrolidines / Q000737:chemistry / Q000378:metabolism*; D064411:Streptomyces rimosus / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*
D001688:Biological Products; D004151:Dipeptides; D011759:Pyrrolidines; D010649:Phenylalanine