The 3D Solution Structure of Thurincin H, a Bacteriocin with Four Sulfur to α‐Carbon Crosslinks

Sit, Clarissa S.; Belkum, Marco J. van; McKay, Ryan; Worobo, Randy W.; Vederas, John C.

doi:10.1002/ange.201102527

Cited by 13 publications

(7 citation statements)

References 15 publications

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“…This “sactionine” linkage is distinct from the C-S bond found in lanthipeptides, which link Cys residues to the β-carbon of dehydrated Ser/Thr residues via a Michael-like nucleophilic addition reaction (Figure 7E). 40 Five sactipeptides have been reported 39 including: subtilosin A, 27 from Bacillus subtilis 168; 41 thurincin H, 28 from B. thuringiensis SF361; 42 sporulation killing factor (SKF, 29 ) from various B. subtilis ; 43 and the two-component thuricin CD (Trn-α, 30 and Trn-β, 31 ) from Bacillus thuringiensis DPC 6431. 44,45 Herein, we discuss recent advances in our understanding of rSAM-mediated thioether bond formation during sactipeptide biosynthesis.…”

Section: Ripp Biosynthetic Reactions Catalyzed By Rsam Enzymesmentioning

confidence: 99%

“…42 Detailed structural characterization of thurincin H revealed that it contains four sactionine linkages between Cys4, Cys7, Cys10, and Cys13 to the α-carbons of Ser28, Thr25, Thr22, and Asn19, respectively. 42 The BGC is comprised of three identical copies of the 40-residue precursor peptide thnA , thnB (rSAM enzyme), thnP (protease), thnD/E/T (three-component ABC transporter), thnR (transcriptional regulator), and thnI (unknown function). Studies using purified ThnB demonstrated that it was responsible for sactionine formation.…”

Section: Ripp Biosynthetic Reactions Catalyzed By Rsam Enzymesmentioning

confidence: 99%

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Radical S-Adenosylmethionine Enzymes Involved in RiPP Biosynthesis

2017

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Ribosomally synthesized and post-translationally modified peptides (RiPPs) display a diverse range of structures and continue to expand as a natural product class. Accordingly, RiPPs exhibit a wide array of bioactivities, such as broad and narrow spectrum growth suppressors, antidiabetics, as well as antinociception and anticancer agents. Owing to these properties, and the complex repertoire of post-translational modifications (PTMs) that give rise to these molecules, RiPP biosynthesis has been intensely studied. RiPP biosynthesis often involves enzymes that perform unique chemistry with intriguing reaction mechanisms, which attract chemists and biochemists alike to study and re-engineer these pathways. One particular type of RiPP biosynthetic enzyme is the so-called radical S-adenosylmethionine (rSAM) enzyme, which utilize radical-based chemistry to install several distinct PTMs. Here, we describe the rSAM enzymes characterized over the past decade that catalyze six reactions types from several RiPP biosynthetic pathways. We present the current state of mechanistic understanding and conclude with possible directions for future characterization of this enzyme family.

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Section: Ripp Biosynthetic Reactions Catalyzed By Rsam Enzymesmentioning

confidence: 99%

Section: Ripp Biosynthetic Reactions Catalyzed By Rsam Enzymesmentioning

confidence: 99%

Radical S-Adenosylmethionine Enzymes Involved in RiPP Biosynthesis

2017

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“…As elucidated by the NMR analysis, one face of the thurincin H hairpin structure is a cluster of hydrophilic amino acid residues. The other hydrophobic residues form prominent patches over the remaining surface of the peptide (Sit et al, 2011). Subtilosin A, a cyclic bacteriocin of B. subtilis, has been characterized both structurally and functionally and possesses some of the same, unique chemical features as thurincin H, including sulfur to a-carbon bonds and a net anionic charge.…”

Section: Discussionmentioning

confidence: 99%

Bactericidal thurincin H causes unique morphological changes inBacillus cereusF4552 without affecting membrane permeability

Wang

Feng

Snyder

et al. 2014

FEMS Microbiol Lett

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Thurincin H is an antilisterial bacteriocin produced by Bacillus thuringiensis SF361. It exhibits inhibitory activity against a wide range of Gram-positive foodborne pathogens and spoilage bacteria including Listeria monocytogenes, B. cereus, and B. subtilis. This hydrophobic, anionic bacteriocin folds into a hairpin structure maintained by four pairs of unique sulfur to α-carbon thioether bonds. As its hydrophobicity and structure are quite different from most archived bacteriocins, this study aimed to elucidate its mode of action and compare it with the mechanisms of other well-characterized bacteriocins. The results indicated that, although bactericidal to B. cereus F4552, thurincin H did not lead to optical density reduction or detectable changes in cell membrane permeability. B. cereus F4552 imaged by scanning electron microscopy after treatment with thurincin H at 32 × MIC showed regular rod-shaped cells, while only cells treated with thurincin H at the elevated levels of 256 × MIC showed loss of cell integrity and rigidity. Both concentrations caused greater than 99% of cell viability reduction. In contrast, nisin caused significant cell membrane permeability at concentration as low as 2 × MIC. These results indicated a difference in the mode of action for thurincin H compared with the generalized pore-forming mechanism of many lantibiotics, such as nisin.

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“…The first reported representative of this RiPP class was subtilosin A [3,4], which was, alongside the sporulation killing factor (SKF) [5] found in Bacillus subtilis 168. The remaining sactipeptides originate from Bacillus thuringiensis DPC 6431 (Trn-a and Trn-b, which together form the two-component bacteriocin thuricin CD) [6,7], and from B. thuringiensis SF361 (thurincin H) [8]. Their known biological functions range from antimicrobial activities against Gram-positive bacteria for thuricin CD, thurincin H and subtilosin A to the spermicidal or hemolytic activities of certain subtilosin A variants [9][10][11][12].…”

Section: Introductionmentioning

confidence: 99%

The PqqD homologous domain of the radical SAM enzyme ThnB is required for thioether bond formation during thurincin H maturation

et al. 2015

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Edited by Miguel De la RosaKeywords: Natural product Ribosomal peptide Sactipeptide Biosynthesis Radical SAM enzyme [4Fe-4S] cluster a b s t r a c t Thurincin H is a 31-residue, ribosomally synthesized bacteriocin originating from the thn operon of Bacillus thuringiensis SF361. It is the only known sactipeptide carrying four thioether bridges between four cysteines and the a-carbons of a serine, an asparagine and two threonine residues.By analysis of the thn operon and use of in vitro studies we now reveal that ThnB is a radical Sadenosylmethionine (SAM) enzyme containing two [4Fe-4S] clusters. Furthermore, we confirm the involvement of ThnB in the formation of the thioether bonds present within the structure of thurincin H. Finally, we show that the PqqD homologous N-terminal domain of ThnB is essential for maturation of the thurincin H precursor peptide, but not for the SAM cleavage activity of ThnB.

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The 3D Solution Structure of Thurincin H, a Bacteriocin with Four Sulfur to α‐Carbon Crosslinks

Cited by 13 publications

References 15 publications

Radical S-Adenosylmethionine Enzymes Involved in RiPP Biosynthesis

Radical S-Adenosylmethionine Enzymes Involved in RiPP Biosynthesis

Bactericidal thurincin H causes unique morphological changes inBacillus cereusF4552 without affecting membrane permeability

The PqqD homologous domain of the radical SAM enzyme ThnB is required for thioether bond formation during thurincin H maturation

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