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Identification of a conserved N-terminal domain in the first module of ACV synthetases.
- Source :
-
MicrobiologyOpen [Microbiologyopen] 2021 Jan; Vol. 10 (1), pp. e1145. Date of Electronic Publication: 2021 Jan 15. - Publication Year :
- 2021
-
Abstract
- The l-δ-(α-aminoadipoyl)-l-cysteinyl-d-valine synthetase (ACVS) is a trimodular nonribosomal peptide synthetase (NRPS) that provides the peptide precursor for the synthesis of β-lactams. The enzyme has been extensively characterized in terms of tripeptide formation and substrate specificity. The first module is highly specific and is the only NRPS unit known to recruit and activate the substrate l-α-aminoadipic acid, which is coupled to the α-amino group of l-cysteine through an unusual peptide bond, involving its δ-carboxyl group. Here we carried out an in-depth investigation on the architecture of the first module of the ACVS enzymes from the fungus Penicillium rubens and the bacterium Nocardia lactamdurans. Bioinformatic analyses revealed the presence of a previously unidentified domain at the N-terminus which is structurally related to condensation domains, but smaller in size. Deletion variants of both enzymes were generated to investigate the potential impact on penicillin biosynthesis in vivo and in vitro. The data indicate that the N-terminal domain is important for catalysis.<br /> (© 2021 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.)
- Subjects :
- 2-Aminoadipic Acid metabolism
Amino Acid Sequence
Amycolatopsis enzymology
Amycolatopsis genetics
Amycolatopsis metabolism
Anti-Bacterial Agents metabolism
Biosynthetic Pathways genetics
Biosynthetic Pathways physiology
Cysteine chemistry
Genetic Variation genetics
Penicillium genetics
Penicillium metabolism
Anti-Bacterial Agents biosynthesis
Penicillium enzymology
Peptide Synthases genetics
Protein Domains genetics
beta-Lactams metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2045-8827
- Volume :
- 10
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- MicrobiologyOpen
- Publication Type :
- Academic Journal
- Accession number :
- 33449449
- Full Text :
- https://doi.org/10.1002/mbo3.1145