Arixanthomycins A–C: Phylogeny-Guided Discovery of Biologically Active eDNA-Derived Pentangular Polyphenols | Zendy

HahkSoo Kang | Zendy; Sean F. Brady | Zendy

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Arixanthomycins A–C: Phylogeny-Guided Discovery of Biologically Active eDNA-Derived Pentangular Polyphenols

Author(s) -

HahkSoo Kang,

Sean F. Brady

Publication year - 2014

Publication title -

acs chemical biology

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 1.899

H-Index - 111

eISSN - 1554-8937

pISSN - 1554-8929

DOI - 10.1021/cb500141b

Subject(s) - biology , chemotype , gene cluster , phylogenetic tree , phylogenetics , gene , natural product , computational biology , heterologous expression , genetics , dna sequencing , biochemistry , botany , recombinant dna , essential oil

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.

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