Thuricin Z: A Narrow‐Spectrum Sactibiotic that Targets the Cell Membrane

Abstract

Sactionine-containing antibiotics (sactibiotics) are ag rowing class of peptide antibiotics belonging to the ribosomally synthesized and post-translationally modified peptide (RiPP) superfamily.W er eport the characterization of thuricin Z, an ovel sactibiotic from Bacillus thuringiensis. Unusually,t he biosynthesis of thuricin Zi nvolves two radical S-adenosylmethionine (SAM) enzymes,T hzC and ThzD. Although ThzC and ThzD are highly divergent from each other,these two enzymes produced the same sactionine ring in the precursor peptide ThzA in vitro.T huricin Ze xhibits narrow-spectrum antibacterial activity against Bacillus cereus.Aseries of analyses,i ncluding confocal laser scanning microscopy, ultrathin-sectioning transmission electron microscopy, scanning electron microscopy, and large-unilamellarvesicle-based fluorescence analysis,s uggested that thuricin Z binds to the bacterial cell membrane and leads to membrane permeabilization.

The manifold roles of microbial ribosomal peptide–based natural products in physiology and ecology

“…, thurincin H from Bacillus thuringiensis SF361, the twopeptide thuricin CD from the human fecal isolate B. thuringiensis DPC 6431, and huazacin or thuricin Z from B. thuringiensis serovar Huazhongensis)(25,32,93,94). They have been found recently in Ruminococcus (ruminococcins from Ruminococcus gnavus isolated from the human microbiota)(32,33) and presumably in Staphylococcus (hyicin from Staphylococcus hyicus 4244).…”

Thuricin Z: A Narrow‐Spectrum Sactibiotic that Targets the Cell Membrane

“…We aim to reveal in detail their biosynthetic pathways (many involve radical SAM enzymes), to discover novel bioactive compounds by genome mining and by bioengineering, and to decipher their modes of action. [5][6][7] www.cjc.wiley-vch.de…”

The SCIFF‐Derived Ranthipeptides Participate in Quorum Sensing in Solventogenic Clostridia

“…Next to BeiA is a radical SAM protein Cbei_4157 (hereafter BeiB) (Figure 1B), which should be responsible for BeiA modification. To validate the function of BeiB, we co‐expressed BeiA and BeiB in E. coli by following the procedures reported previously, [ 1,23,24 ] and BeiA was also expressed alone in E. coli for comparative analysis. High resolution mass spectrometry (HR‐MS) analysis revealed that BeiA obtained from co‐expression with BeiB is 2 Da less than BeiA expressed alone, suggesting formation of a thioether crosslink ( Figure 2 A).…”