Open AccessPhormidepistatin from the Cyanobacterium UIC 10484: Assessing the Phylogenetic Distribution of the Statine Pharmacophore
Author(s) -
Peter Sullivan,
Aleksej Krunić,
Lydia J Davis,
Hwan Seung Kim,
Joanna E. Burdette,
Jimmy Orjala
Publication year - 2021
Publication title -
journal of natural products
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.976
H-Index - 139
eISSN - 1520-6025
pISSN - 0163-3864
DOI - 10.1021/acs.jnatprod.1c00334
Subject(s) - pharmacophore , stereochemistry , amino acid , cyanobacteria , moiety , biology , depsipeptide , phylogenetic tree , chemistry , biochemistry , genetics , gene , bacteria
A new linear lipopeptide, phormidepistatin ( 1 ), containing an epi-statine amino acid was isolated from cf. Phormidium sp. strain UIC 10484. The planar structure was elucidated by 1D and 2D NMR experimentation. The relative configuration was determined by J -based configurational analysis and the absolute configuration by advanced Marfey's analysis. Given that the statine moiety is an established pharmacophore known to inhibit aspartic proteases, phormidepistatin was evaluated against cathepsin D and displayed limited activity. With 1 containing a statine-like moiety, we sought to assess the distribution of this γ-amino acid within the phylum Cyanobacteria. In-depth MS/MS analysis identified the presence of phormidepistatin in cf. Phormidium sp. UIC 10045 and cf. Trichormus sp. UIC 10039. A structure database search identified 33 known cyanobacterial metabolites containing a statine or statine-like amino acid and, along with phormidepistatin, were grouped into 10 distinct compound classes. A phylogenetic tree was built comprising all cyanobacteria with established 16S rRNA sequences known to produce statine or statine-like-containing compound classes. This analysis suggests the incorporation of the γ-amino acid into secondary metabolites is taxonomically widespread within the phylum. Overall, it is our assessment that cyanobacteria are a potential source for statine or statine-like-containing compounds.