title: Arixanthomycins A-C: Phylogeny-guided discovery of biologically active eDNA-derived pentangular polyphenols.
abstract: Soil microbiomes are a rich source of uncharacterized natural product biosynthetic gene clusters. Here we use short conserved biosynthetic gene sequences (natural product sequence tags) amplified from soil microbiomes as phylogenetic markers to correlate genotype to chemotype and target the discovery of novel bioactive pentangular polyphenols from the environment. The heterologous expression of an environmental DNA-derived gene cluster (the ARX cluster), whose ketosynthase beta (KSβ) sequence tag was phylogenetically distinct from any known KSβ sequence, led to the discovery of the arixanthomycins. Arixanthomycin A (1) exhibits potent antiproliferative activity against human cancer cell lines.
authors.affiliation: Howard Hughes Medical Institute, Laboratory of Genetically Encoded Small Molecules, The Rockefeller University , 1230 York Avenue, New York, New York 10065, United States.
authors.forename: Hahk-Soo
authors.initials: HS
authors.lastname: Kang
authors.forename: Sean F
authors.initials: SF
authors.lastname: Brady
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D019295:Computational Biology; D004247:DNA / Q000235:genetics*; D055808:Drug Discovery; D006801:Humans; D054892:Metagenome; D015394:Molecular Structure; D005810:Multigene Family; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010802:Phylogeny; D061065:Polyketides / Q000737:chemistry / Q000494:pharmacology*; D059808:Polyphenols / Q000737:chemistry / Q000494:pharmacology*; D017422:Sequence Analysis, DNA; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D061065:Polyketides; D059808:Polyphenols; C000600622:arixanthomycin A; C000600623:arixanthomycin B; C000600624:arixanthomycin C; D004247:DNA
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