Epidermin: sequencing of a heterodet tetracyclic 21‐peptide amide antibiotic

Abstract

Epidermin is a large peptide antibiotic, which is synthesized in the ribosome via a precursor protein, followed by enzymatic modifications. It was isolated from the culture filtrate of Staphylococcus epidermidis Tü 3298 by adsorption on Amberlite XAD‐8. The basic heneicosapeptide amide was chromatographed on Sephadex LH‐20 and purified to homogeneity via multiplicative counter‐current distributions in one acidic and one neutral system. Tryptic digestion gave the soluble N‐terminal fragment epidermin‐(1–13)‐peptide (P1) and the insoluble C‐terminal fragment 2‐oxobutyryl‐epidermin‐(15–21)‐peptide amide (P2), each possessing two sulfide ring systems. The heterodetic rings consisted of meso‐lanthionine and (2S,3S,6R)‐3‐methyllanthionine (P1), meso‐lanthionine and C‐terminally the new amino acid S‐(2‐aminovinyl)‐D‐cysteine (P2). The complex sequence was elucidated via a combination of desulfurization with Raney nickel, enzymatic and acidolytic degradations, gas‐phase sequencing, fast‐atom bombardment and field‐desorption mass spectrometry and NMR spectroscopy. Copyright © 1986, Wiley Blackwell. All rights reserved