Engineering dehydrated amino acid residues in the antimicrobial peptide nisin.

Kuipers, Oscar P.; Rollema, Harry S.; Yap, Wyanda M. G. J.; Boot, Hein J.; Siezen, Roland J.; Vos, Willem M. de

doi:10.1016/s0021-9258(18)35771-5

Cited by 179 publications

(38 citation statements)

References 24 publications

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“…A new quartet signal around 6.6 ppm emerges in the downfield region (aromatic and vinyl proton signal region, 6.0-8.0 ppm) of the 1 H-NMR spectrum of SpvC-reacted peptide compared with that of the control peptide (Figure 1D). The chemical shift and multiplicity of the new signal corresponds to the vinyl proton signal of b-methyldehydroalanine as previously reported (Kuipers et al, 1992). These results provide direct evidence for the presence of Ca = Cb structure in OspF/ SpvC-processed phosphothreonine in Erk2 and substantiate the proposed phosphothreonine lyase activity of the OspF family of effectors.…”

Section: Resultssupporting

confidence: 87%

Structural Insights into the Enzymatic Mechanism of the Pathogenic MAPK Phosphothreonine Lyase

et al. 2007

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The OspF family of phosphothreonine lyase, including SpvC from Salmonella, irreversibly inactivates the dual-phosphorylated host MAPKs (pT-X-pY) through beta elimination. We determined crystal structures of SpvC and its complex with a phosphopeptide substrate. SpvC adopts a unique fold of alpha/beta type. The disordered N terminus harbors a canonical D motif for MAPK substrate docking. The enzyme-substrate complex structure indicates that recognition of the phosphotyrosine followed by insertion of the threonine phosphate into an arginine pocket places the phosphothreonine into the enzyme active site. This requires the conformational flexibility of pT-X-pY, which suggests that p38 (pT-G-pY) is likely the preferred physiological substrate. Structure-based biochemical and enzymatic analysis allows us to propose a general acid/base mechanism for beta elimination reaction catalyzed by the phosphothreonine lyase. The mechanism described here provides a structural understanding of MAPK inactivation by a family of pathogenic effectors conserved in plant and animal systems and may also open a new route for biological catalysis.

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Section: Resultssupporting

confidence: 87%

Structural Insights into the Enzymatic Mechanism of the Pathogenic MAPK Phosphothreonine Lyase

et al. 2007

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“…The structural differences in Viscosinand Amphisin-like CLDPs, sharing the same 3HDA fatty acid moiety are all also caused by single amino acid replacements in the peptide moiety. However, in lantibiotics, small-sized antimicrobial peptides which are active against a broad range of Gram-positive bacteria, the uncommon amino acid residues dehydroalanine (Dha) and dehydrobutyrine (Dhb) are formed post-translationally from Ser and Thr residues, respectively [22]. This is also a distinct possibility for the diversity of PPZPM members.…”

Section: Ms/msmentioning

confidence: 99%

PPZPMs - a Novel Group of Cyclic Lipodepsipeptides Produced by thePhytophthora alniAssociated StrainPseudomonassp. JX090307 -the Missing Link between the Viscosin and Amphisin Group

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Hentschel

Zaspel

et al. 2014

Natural Product Communications

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The closely related to the Pseudomonas orientalis strain Pseudomonas sp. acc. no. JX090307 was isolated from hyphae of the phytopathogenic oomycete Phytophthora alni spp. alni. In in-vitro antagonistic tests, the living bacterium JX090307 and its cell extract showed antibiosis activity against different fungal pathogens of forest tree species, particularly against Verticillium dahliae and some strains of P. alni ssp. alni. Investigating the cell extract of JX090307 by means of LC-ESI-Q-TOF-MS and-MS/MS techniques, more than 30 cyclic lipodepsipeptids (CLPs) were found. 24 of them belong to a novel group of CLPs named PPZPM. The cyclic lipodepsidecapeptides PPZPMs are composed of a β-hydroxy fatty acid linked to a peptide part comprising 10 amino acids, where 8 of them are organized in a cyclic structure. PPZPMs differ from members of the Viscosin and Amphisin group by the number of amino acids forming the cyclic structure. The two main components, PPZPM-1a and PPZPM-2a, were investigated additionally by means of NMR spectroscopy.

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“…Nisin is the prototypical lantibiotic that exhibits potent broad-spectrum antimicrobial activity against a wide array of pathogens. Several bioengineering studies of wild-type nisin A have been carried out to improve its antimicrobial properties and functions (Kuipers et al 1992;Karakas Sen et al 1999;van Kraaij et al 2000;Rink et al 2007). Numerous elegant studies have established that the nisin A biosynthetic/modification machinery demonstrates tolerance to a broad range of substrates (Kluskens et al 2005;Rink et al 2007;Majchrzykiewicz et al 2010).…”

Section: Discussionmentioning

confidence: 99%

Nisin variants from Streptococcus and Staphylococcus successfully express in NZ9800

et al. 2021

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Aims: Increases in antimicrobial resistance have meant that the antimicrobial potential of lantibiotics is now being investigated irrespective of the nature of the producing organism. The aim of this study was to investigate whether natural nisin variants produced by non-Generally Recognized as Safe (GRAS) strains, such as nisin H, nisin J and nisin P, could be expressed in a wellcharacterized GRAS host. Methods and Results: This study involved cloning the nisin A promoter and leader sequence fused to nisin H, nisin J or nisin P structural gene sequences originally produced by Streptococcus hyointestinalis DPC 6484, Staphylococcus capitis APC 2923 and Streptococcus agalactiae DPC 7040, respectively. This resulted in their expression in Lactococcus lactis NZ9800, a genetically modified strain that does not produce nisin A. Conclusions: Induction of the nisin controlled gene expression system demonstrates that these three nisin variants could be acted on by nisin A machinery provided by the host strain. Significance and Impact of the Study: Describes the first successful heterologous production of three natural nisin variants by a GRAS strain, and demonstrates how such systems could be harnessed not only for lantibiotic production but also in the expansion of their structural diversity and development for use as future biotherapeutics.

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Engineering dehydrated amino acid residues in the antimicrobial peptide nisin.

Cited by 179 publications

References 24 publications

Structural Insights into the Enzymatic Mechanism of the Pathogenic MAPK Phosphothreonine Lyase

Structural Insights into the Enzymatic Mechanism of the Pathogenic MAPK Phosphothreonine Lyase

PPZPMs - a Novel Group of Cyclic Lipodepsipeptides Produced by thePhytophthora alniAssociated StrainPseudomonassp. JX090307 -the Missing Link between the Viscosin and Amphisin Group

Nisin variants from Streptococcus and Staphylococcus successfully express in NZ9800

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