EC Number   |
General Information |
Reference |
|---|
   6.2.1.67 | metabolism |
proposed biosynthetic pathway for saframycin A involving genes sfmA, sfmB, and sfmC, overview |
-, 761376 |
| 6.2.1.67 | metabolism |
Pseudomonas aeruginosa toxin L-2-amino-4-methoxy-trans-3-butenoicacid (AMB)is a non-proteinogenic amino acid which is toxic for prokaryotes and eukaryotes. Production of AMB requires a five-gene cluster encoding a putative LysE-type transporter (AmbA), two non-ribosomal peptide synthetases (AmbB and AmbE, EC 6.2.1.67 and EC 6.2.1.68, respectively), and two iron(II)/alpha-ketoglutarate-dependent oxygenases (AmbC and AmbD). Bioinformatics analysis predicts one thiolation (T) domain for AmbB and two T domains (T1 and T2) for AmbE, suggesting that AMB is generated by a processing step from a precursor tripeptide assembled on a thiotemplate. The AmbB substrate is identified to be L-alanine (L-Ala), while the T1 and T2 domains of AmbE are loaded with L-glutamate (L-Glu) and L-Ala, respectively. Loading of L-Ala at T2 of AmbE occurs only in the presence of AmbB, indicative of a trans loading mechanism. In vitro assays performed with AmbB and AmbE result in the dipeptide L-Glu-L-Ala at T1 and the tripeptide L-Ala-L-Glu-L-Ala attached at T2. When AmbC and AmbD are included in the assay, these peptides are no longer detected. Instead, an L-Ala-AMB-L-Ala tripeptide is found at T2, importance of flanking L-Ala residues in the precursor tripeptide |
-, 761151 |
| 6.2.1.67 | metabolism |
the tripeptide backbone of phosphinothricin (PT) tripeptide (PTT), a compound with herbicidal activity from Streptomyces viridochromogenes, is assembled by three stand-alone peptide synthetase modules. The enzyme PhsA (66 kDa) recruits the PT-precursor N-acetyl-demethylphosphinothricin (N-Ac-DMPT), whereas the two alanine residues of PTT are assembled by the enzymes PhsB and PhsC (129 and 119 kDa, respectively). During or after assembly, the N-Ac-DMPT residue in the peptide is converted to PT by methylation and deacetylation. Both phsB and phsC appear to be cotranscribed together with two other genes from a single promoter and they are located at a distance of 20 kb from the gene phsA, encoding PhsA, in the PTT biosynthesis gene cluster of Streptomyces viridochromogenes |
-, 760352 |
| 6.2.1.67 | more |
enzyme AmbB presents the typical modular structure of non-ribosomal peptide synthetases (NRPSs) |
-, 761151 |
| 6.2.1.67 | more |
the biosynthetic gene cluster for SFM-A is cloned and localized to a 62-kb contiguous DNA region. Sequence analysis revealed 30 genes that constitute the SFM-A gene cluster, encoding an unusual nonribosomal peptide synthetase (NRPS) system and tailoring enzymes and regulatory and resistance proteins. The results of substrate prediction and in vitro characterization of the adenylation specificities of this NRPS system support the hypothesis that the last module acts in an iterative manner to form a tetrapeptidyl intermediate and that the co-linearity rule does not apply |
-, 761376 |
| 6.2.1.67 | physiological function |
the enzyme is involved in biosynthesis of Pseudomonas aeruginosa toxin L-2-amino-4-methoxy-trans-3-butenoicacid (AMB), which proceeds via a precursor tripeptide. Identification of the building blocks of AMB biosynthesis and modelling, overview |
-, 761151 |
| 6.2.1.67 | physiological function |
the enzyme is involved in the synthesis of saframycin A (SFM-A) by Streptomyces lavendulae strain NRRL 11002. The compound belongs to the tetrahydroisoquinoline family of antibiotics. The backbone of SFM-A is derived from one Ala, one Gly, and two Tyr residues, suggesting that it is of tetrapeptide origin. SfmA, SfmB, and SfmC constitute an nonribosomal peptide synthetase (NRPS) system |
-, 761376 |
| 6.2.1.67 | physiological function |
the tripeptide backbone of phosphinothricin (PT) tripeptide (PTT), a compound with herbicidal activity from Streptomyces viridochromogenes, is assembled by three stand-alone peptide synthetase modules. The enzyme PhsA (66 kDa) recruits the PT-precursor N-acetyl-demethylphosphinothricin (N-Ac-DMPT), whereas the two alanine residues of PTT are assembled by the enzymes PhsB and PhsC (129 and 119 kDa, respectively). During or after assembly, the N-Ac-DMPT residue in the peptide is converted to PT by methylation and deacetylation. PhsB and PhsC represent single nonribosomal peptide synthetase elongation modules lacking a thioesterase domain |
-, 760352 |
| 6.2.1.67 | physiological function |
the tripeptide backbone of phosphinothricin (PT) tripeptide (PTT), a compound with herbicidal activity from Streptomyces viridochromogenes, is assembled by three stand-alone peptide synthetase modules. The enzyme PhsA (66 kDa) recruits the PT-precursor N-acetyl-demethylphosphinothricin (N-Ac-DMPT), whereas the two alanine residues of PTT are assembled by the enzymes PhsB and PhsC (129 and 119 kDa, respectively). During or after assembly, the N-Ac-DMPT residue in the peptide is converted to PT by methylation and deacetylation. PhsB and PhsC represent single nonribosomal peptide synthetase elongation modules lacking a thioesterase domain. Gene inactivations, genetic complementations, determinations of substrate specificity of the heterologously produced proteins, and comparison of PhsC sequence with the N-terminus of the alanine-activating nonribosomal peptide synthetase PTTSII from Streptomyces viridochromogenes confirm the role of the two genes in the bialanylation of Ac-DMPT. The lack of an integral thioesterase domain in the PTT assembly system points to product release possibly involving two type II thioesterase genes (the1 and the2) located in the PTT gene cluster alone or in conjunction with another mechanism of product release |
-, 760352 |
