1.D.24.1.1
Polytheonamide B from a bacterium symbiont of Theonella swinhoei pTSMAC1. It is of 145 aas with 1 TMS near the C-terminus of the protein. Antimicrobial peptide active against Gram-positive bacteria (MIC=4->125 ug/ml) (Freeman et al. 2012).It may act by forming transmembrane ion channels, since the peptide rapidly depolarizes the bacterial cytoplasmic membrane, simultaneously decreasing the membrane potential and intracellular potassium contents. The name 'proteusin' was inspired by Proteus, a Greek shape-shifting sea god. Compared to polytheonamide B, polytheonamide A has an additional sulfoxide moiety at Met-141, which arises from spontaneous oxidation during polytheonamide isolation. The potent cytotoxicity of PolyA against MCF-7 cancer cells originates from its two ion transport functions. Compound 1 depolarizes the plasma membrane and neutralizes acidic lysosomes. Xue et al. 2023 described how these two functions can be uncoupled by designing and synthesizing new analogues.