Characterization of the Tychonamide Biosynthetic Pathway in the Recently Described Cyanobacterial Species Floridanema aerugineum

Secondary metabolite profiling of a recently described new cyanobacterial species Floridanema aerugineum identified abundant amounts of the polyketide-peptide tychonamide A. Investigation of the biosynthetic gene clusters in the F. aerugineum genome identified a putative tychonamide biosynthetic gene cluster with module and domain architecture consistent with the tychonamide A structure. High resolution liquid chromatography–mass spectrometry/MS (LC-MS/MS) identified new tychonamide analogs C-E (1–3), and bioactivity predictions led us to test the protease inhibition activities of the tychonamides. The results of this analysis illustrated the biosynthesis of the 3-amino-2,5,7-trihydroxy-8-phenyloctanoic acid moiety (Atpoa) in tychonamide A, further deduced the absolute configuration of tychonamide A, and uncovered new biological activities (human neutrophil elastase inhibition) that may be relevant in environmental science and pharmaceutical development.