Genome-Guided Discovery of Floridanemastatin, a Statine-Containing Polyketide-Peptide from the Cyanobacterium Floridanema evergladense

Abstract

Abstract We report the genome-guided discovery, isolation, and characterization of floridanemastatin (1), a previously undescribed statine-containing polyketide−peptide from Floridanema evergladense BLCC-F167. Examination of the biosynthetic gene clusters in the F.evergladense genome revealed a hybrid PKS−NRPS biosynthetic gene cluster featuring an NRPS module followed by a PKS ketoextension and ketoreductase domain arrangement diagnostic of statine biosynthesis. Guided by this prediction, LC−MS-based analysis of cultured biomass led to the isolation of floridanemastatin. High-resolution mass spectrometry and comprehensive 1D and 2D NMR spectroscopy defined a polyketide−peptide scaffold incorporating serine, proline, a leucine-derived amino alcohol, and a statine-like residue identified as 4-amino-3-hydroxy-(4-hydroxyphenyl)pentanoic acid. Connectivity and residue assignments were consistent with the predicted biosynthetic logic of the gene cluster, including reductive chain termination to yield an alcohol. Although the statine pharmacophore and in silico target prediction suggested cathepsin D as a plausible target, enzymatic evaluation indicated that apparent inhibition was attributable to nonspecific aggregation under the assay conditions. These findings demonstrate the utility of biosynthetic gene cluster architecture for prospecting statine-containing cyanobacterial natural products and further highlights the genus Floridanema as a source of chemically distinctive specialized metabolites.

The authors' abstract, as published at the source. Journal of Natural Products, 2026 · DOI ↗