Thiopeptide Biosynthesis Featuring Ribosomally Synthesized Precursor Peptides and Conserved Posttranslational Modifications

Liao, Rijing; Duan, Lian; Lei, Chun; Pan, Hai‐Xue; Ding, Ying; Zhang, Qi; Chen, Daijie; Shen, Ben; Yu, Yi; Li, Wen

doi:10.1016/j.chembiol.2009.01.007

Cited by 181 publications

(237 citation statements)

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“…In this regard, the chemistry described by these systems is very different. In clostriodiolysin S, an amide carbonyl undergoes activation, as is the case for microcin B17, patellamide, goadsporin, and the recently described thiopeptide family (13)(14)(15)(16)27). Because ClosA contains a C-terminal asparagine, in addition to several Ser, Thr, B, shown is the genetic complementation of Clos genes in GAS M1 Sag mutants.…”

Section: Closa-d Genetic Complementation Studies In Groupmentioning

confidence: 99%

“…ClosBCD resembles the McbBCD-modifying proteins found in the Escherichia coli microcin B17 system and the Prochloron didemni patDG genes of the patellamide biosynthetic gene cluster. This family of natural product toxins was recently shown by several groups to include the thiopeptides, which are nearly ubiquitous in soil-dwelling Bacillus and Streptomyces bacteria (12)(13)(14)(15)(16). In the microcin B17 system, McbB, -C, and -D were shown to be necessary and sufficient for the installation of heterocyclic moieties on C-terminal serine and cysteine residues of the McbA substrate.…”

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confidence: 99%

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Clostridiolysin S, a Post-translationally Modified Biotoxin from Clostridium botulinum

Gonzalez

Lee

Hensler

et al. 2010

Journal of Biological Chemistry

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Through elaboration of its botulinum toxins, Clostridium botulinum produces clinical syndromes of infant botulism, wound botulism, and other invasive infections. Using comparative genomic analysis, an orphan nine-gene cluster was identified in C. botulinum and the related foodborne pathogen Clostridium sporogenes that resembled the biosynthetic machinery for streptolysin S, a key virulence factor from group A Streptococcus responsible for its hallmark ␤-hemolytic phenotype. Genetic complementation, in vitro reconstitution, mass spectral analysis, and plasmid intergrational mutagenesis demonstrate that the streptolysin S-like gene cluster from Clostridium sp. is responsible for the biogenesis of a novel post-translationally modified hemolytic toxin, clostridiolysin S.Microbial virulence and survival are often defined by metabolic output. Among the many molecular species used to give a competitive advantage are hydrogen peroxide, genetically encoded small molecules, siderophores, proteins, and bacteriocins (1, 2). Streptolysin S (SLS) 2 is a well known hemolytic/ cytolytic, ribosomally encoded bacteriocin and virulence factor group A Streptococcus (GAS) (3)(4)(5). To this day, the characteristic ␤-hemolytic phenotype observed on blood agar plates is used as a clinical diagnostic tool for GAS identification. GAS is best known as the agent of acute pharyngitis (strep throat) but also may cause invasive infections, including necrotizing fasciitis and toxic shock syndrome. In the 100-year history of our knowledge of streptococcal bacteria, the precise chemical structure of this toxin has remained elusive, although the discovery of its biosynthetic gene cluster more than a decade ago (4) has guided investigations into its post-translational modification and likely heterocyclic nature (6, 7).Through recent comparative genomic analysis, an SLS-type gene cluster was identified in clostridia species including Clostridium botulinum and Clostridium sporogenes, two diseasecausing bacteria known to endanger food supplies (8 -10). Similar gene clusters were found in Staphylococcus aureus RF122, Bacillus thuringiensis, Streptococcus iniae, and Listeria monocytogenes 4b. The L. monocytogenes 4b strain is the primary serotype and causative agent for outbreaks of listeriosis (11). The S. aureus RF122 strain is responsible for bovine mastitis. S. iniae is a cytotoxic fish pathogen. This suggests that a shared metabolic output of these pathogens including SLS-like toxins may contribute to their pathogenic potential (11).Each of these SLS family gene clusters contains a similar set of genes. For instance, in C. botulinum and C. sporogenes, the closA-I genes are related by sequence to sagA-I from GAS (see Fig. 1A). Of these genes, ClosF is a protein of unknown function. ClosG, -H, and -I are ABC transporters and therefore are likely to be responsible for exporting the mature hemolytic product. ClosA is the prepropeptide (structural peptide) that is post-translationally modified to form the propeptide. ClosE has been annotated as an i...

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Section: Closa-d Genetic Complementation Studies In Groupmentioning

confidence: 99%

mentioning

confidence: 99%

Clostridiolysin S, a Post-translationally Modified Biotoxin from Clostridium botulinum

Gonzalez

Lee

Hensler

et al. 2010

Journal of Biological Chemistry

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“…The LanB dehydratases are 115-120 kDa proteins that do not share homology with the dehydratases from classes II-IV lanthipeptides or other proteins in the databases. Genes encoding homologous LanB-like enzymes are also present in the gene clusters of nonlantibiotic peptide natural products, such as the thiopeptides (16)(17)(18)(19) and goadsporin (20). These proteins are also believed to be dehydratases.…”

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confidence: 99%

In vitro activity of the nisin dehydratase NisB

Garg¹,

Salazar-Ocampo

Donk

2013

Proc. Natl. Acad. Sci. U.S.A.

108

167

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The biosynthesis of several classes of ribosomally synthesized and posttranslationally modified peptides involves dehydration of serine and threonine residues. For class I lantibiotics, thiopeptides, and goadsporin, this dehydration is catalyzed by lanthionine biosynthetic enzyme B (LanB) or LanB-like proteins. Although LanB proteins have been studied since 1992, in vitro reconstitution of their dehydration activity has been elusive. We show here the in vitro activity of the dehydratase involved in the biosynthesis of the food preservative nisin (NisB). In vitro, NisB dehydrated its substrate peptide NisA eight times in the presence of glutamate, ATP, Mg 2+ , and the ribosomal/ membrane fraction of bacterial cell extract. Mutation of 23 highly conserved residues of NisB identified a number of amino acids that are essential for dehydration activity. In addition, these mutagenesis studies identified three mutants, R786A, R826A, and H961A, that result in multiple glutamylations of the NisA substrate. Glutamylation was observed during both Escherichia coli coexpression of NisA with these mutants and in vitro assays. Treatment of the glutamylated substrate with WT NisB results in dehydrated NisA, suggesting that the glutamylated peptide is an intermediate in dehydration. Collectively, these studies suggest that dehydration involves glutamylation of the side chains of Ser and Thr followed by elimination. The latter step has precedent in the virginiamycin resistance protein virginiamycin B lyase. These studies will facilitate investigation of other LanB proteins involved in the biosynthesis of lantibiotics, thiopeptides, and goadsporin.

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“…ÂПЛиÂ N-МеТиЛ-N-НIТРÎ-N-НIТРÎЗÎГУАНIДиНУ ТА N-МеТиЛ-N-НIТРÎЗÎМеТиЛСечÎÂиНи... попередíèк сèíтезуєтьсÿ íà рèбосоìàх [11], à тàкож стâореíо сèстеìу клоíуâàííÿ геíіâ у клітèíàх S. sioyaensis [13]. Уìоâою успішíого âèâчеííÿ зàкоíоìірíостей біосèíтезу сіоìіöèíу, à тàкож отрèìàííÿ його біотехíологічíèх продуöеíтіâ з âèсокèì ріâíеì àíтèбіотèчíої àктèâíості, є стâореííÿ сèстеìè селекöії ìутàíтіâ S. sioyaensis.…”

Section: ìікробіоëоãія і біотеõноëоãія ¹ 6/2009unclassified

N-Methyl-N'-Nitro-N-Nitrosoguanidine and N-Methyln-Nitrosomethylurea Influence on Antibiotic Activity of Streptomyces Sioyaensis Lv81

Грубський¹,

Аравіцька²,

Мироновський³

et al. 2009

Microbiology&Biotechnology

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Thiopeptide Biosynthesis Featuring Ribosomally Synthesized Precursor Peptides and Conserved Posttranslational Modifications

Cited by 181 publications

References 19 publications

Clostridiolysin S, a Post-translationally Modified Biotoxin from Clostridium botulinum

Clostridiolysin S, a Post-translationally Modified Biotoxin from Clostridium botulinum

In vitro activity of the nisin dehydratase NisB

N-Methyl-N'-Nitro-N-Nitrosoguanidine and N-Methyln-Nitrosomethylurea Influence on Antibiotic Activity of Streptomyces Sioyaensis Lv81

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