Streptocollin, a Type IV Lanthipeptide Produced by Streptomyces collinus Tü 365

Abstract

Lanthipeptides are ribosomally synthesized and post‐translationally modified microbial secondary metabolites. Here, we report the identification and isolation of streptocollin from Streptomyces collinus Tü 365, a new member of class IV lanthipeptides. Insertion of the constitutive ermE* promoter upstream of the lanthipeptide synthetase gene stcL resulted in peptide production. The streptocollin gene cluster was heterologously expressed in S. coelicolor M1146 and M1152 with 3.5‐ and 5.5‐fold increased yields, respectively. The structure and ring topology of streptocollin were determined by high resolution MS/MS analysis. Streptocollin contains four macrocyclic rings, with one lanthionine and three methyllanthionine residues. To the best of our knowledge, this is the first report on the isolation of a class IV lanthipeptide in preparative amounts, and on the successful heterologous expression of a class IV lanthipeptide gene cluster.

New Insights into the Biosynthetic Logic of Ribosomally Synthesized and Post-translationally Modified Peptide Natural Products

“…A third route to (Me)Lan formation in class III and IV lanthipeptides features the use of trifunctional enzymes composed of a central Ser/Thr kinase domain, an N-terminal phosphoSer/phosphoThr lyase domain, and a C-terminal cyclization domain (Goto et al, 2010, Iftime et al, 2015, Jungmann et al, 2014, Müller et al, 2010). Hence, these enzymes use the same chemical strategy as the class II synthetases, but like the class I dehydratases, activation of the Ser/Thr hydroxyl groups and elimination of the activating group is achieved in separate active sites.…”

Roseocin, a novel two‐component lantibiotic from an actinomycete

“…Classes II, III and IV lanthipeptide BGCs encode a single lanthionine synthetase instead of a separate dehydratase, and cyclase enzyme for the lanthionine ring formation (Arnison et al, ). The Classes III and IV lanthipeptides majorly display bioactivities other than antimicrobial, like morphogenetic (Ueda et al, ), antiviral, antiallodynic (Férir et al, ), antinociceptive (Iorio et al, ) and antidiabetic activities (Iftime et al, ). The Class II lantibiotics are processed by a single lanthionine synthetase and are also the most studied lantibiotics by heterologous expression (Zhang, Chen, Bruner, & Ding, ).…”

Complete genome sequence of Bacillus subtilis BSD-2, a microbial germicide isolated from cultivated cotton

“…After annotation, we identified genes or gene clusters related with the biosynthesis of some antifungal secondary metabolites, and found out full pathway of surfactin, bacilysin, subtilosin A, Tas A and partial pathway of bacillibactin. Using BAGEL 3 and antiSMASH 3.0 online prediction software, we got a potential class IV lanthipeptide (Iftime et al, 2015) biosynthetic pathway.…”