[45] Tyrocidine synthetase system

Lee, Sung G.; Lipmann, Fritz

doi:10.1016/0076-6879(75)43121-4

Cited by 86 publications

(68 citation statements)

References 8 publications

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“…Examples are the syntheses of peptide antibiotics in Bacilli sp. (2)(3)(4), Streptomyces sp. (5-7), and Amycolatopsis sp.…”

mentioning

confidence: 99%

“…Over-representation of one or two amino acids within a peptide is a characteristic feature of nonribosomally constructed peptide antibiotics (4,5). As there exists an intriguing possibility that the core protein is indeed constructed at least in part by a nonribosomal peptide synthesis pathway, we considered whether some of the alanine residues might be in the D-form, a hallmark feature of nonribosomal synthesis of peptide antibiotics (11,12).…”

mentioning

confidence: 99%

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Presence of D-Alanine in an Endopeptidase from Streptococcus pyogenes

Lee

Fischetti

2003

Journal of Biological Chemistry

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D-Amino acids are commonly found in peptide antibiotics and the cell wall peptidoglycan of bacterial cell walls but have not been identified in proteins or enzymes. Here we report the presence of 6 -7 D-alanine residues in an endopeptidase of Streptococcus pyogenes, a unique enzyme involved in surface protein attachment that we term LPXTGase. Using D-amino acid oxidase coupled with catalase for the deamination of D-alanine to pyruvic acid (a conversion unique to D-alanine), we were able to identify [ 14 C]pyruvic acid in a [ 14 C]alaninelabeled preparation of purified LPXTGase, which represents 27% of the amino acid composition. Because Damino acids are not accommodated in ribosomal peptide synthesis, these results suggest that the same process used in assembling peptide antibiotics or a yet unidentified mechanism may synthesize the core protein of this endopeptidase.In our previous report we described the unusual properties of an endopeptidase termed LPXTGase purified from Streptococcus pyogenes (1). This membrane-associated enzyme cleaves a common sequence motif, LPXTG, found near the C termini of precursor proteins programmed to be displayed on the cell surface and linked to the cell wall peptidoglycan. We discovered that the LPXTGase is highly glycosylated and contains hydrophobic amino acids with unusually high masses, which are not among the 20 common amino acids present in ribosomally translated proteins. The presence of unusual amino acids indicated the possibility that the core protein of the enzyme might be constructed entirely or in part through the well characterized nonribosomal peptide synthesis pathway, where amino acids are assembled into a peptide on amino acid-activating multienzyme templates. Examples are the syntheses of peptide antibiotics in Bacilli sp. (2-4), Streptomyces sp. (5-7), and Amycolatopsis sp. (8, 9), synthesis of a phytoionophore in Pseudomonas syringae (10), and synthesis of the immunosuppressant cyclosporin A in the fungus Tolypocladium niveum (11). Unusual amino acids could also be incorporated into the ribosomally translated core protein through post-translational modifications, however. Another unusual feature of the core protein of LPXTGase is that only seven different amino acids represent 93% of the 61 common residues present in the core protein. It is particularly striking that alanine accounts for nearly 40% of the common amino acids found in the protein.Over-representation of one or two amino acids within a peptide is a characteristic feature of nonribosomally constructed peptide antibiotics (4, 5). As there exists an intriguing possibility that the core protein is indeed constructed at least in part by a nonribosomal peptide synthesis pathway, we considered whether some of the alanine residues might be in the D-form, a hallmark feature of nonribosomal synthesis of peptide antibiotics (11,12). This prompted us to search for the presence of D-alanine in the core protein of LPXTGase. In this report, we present strong evidence that alanine in the D-isoform is present in...

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“…Examples are the syntheses of peptide antibiotics in Bacilli sp. (2)(3)(4), Streptomyces sp. (5-7), and Amycolatopsis sp.…”

mentioning

confidence: 99%

mentioning

confidence: 99%

Presence of D-Alanine in an Endopeptidase from Streptococcus pyogenes

Lee

Fischetti

2003

Journal of Biological Chemistry

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“…For instance, presence of a smaller protein, split off by a factor in the fermentation broth, which acts as a carrier of the phosphopantetheine arm in tyrocidine synthetase, was reported [9].…”

Section: Discussionmentioning

confidence: 99%

Tryptic cleavage of enzyme a in bacitracin synthetase

Frøyshov¹,

Mathiesen²

1979

FEBS Letters

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“…104 Structure-guided alignments of bacterial A domain sequences can be used to predict the residues that line the substrate binding pocket of these enzymes. The predicted amino acid residues can then be used to predict the substrate specificity of the A domains of novel bacterial NRPSs, relying on comparisons with a large database of A domains with known substrate specificities.…”

Section: Adenylation Domainsmentioning

confidence: 99%

“…The activities of both adenylation domains of FeESYN (A 1 and A 2 ) were characterized using the ATP-PP i exchange reaction. 104 However, further assays that measure the covalent loading of the substrates (D-Hiv and L-Val) on the T domains of the expressed protein fragments as hydroxyacyl or aminoacyl thioesters were unsuccessful. This suggested that the phosphopantetheinyl transferase of the E. coli fatty acid synthase does not recognize the FeESYN as its substrate.…”

Section: Enniatin Synthetase Gene Fragmentsmentioning

confidence: 99%