The nonproteinogenic amino acid capreomycidine is the signature residue found in the tuberactinomycin family of antitubercular peptide antibiotics and an important element of the pharmacophore. Recombinant VioG, a single-module peptide synthetase from the viomycin gene cluster cloned from Streptomyces vinaceus (ATCC11861), specifically activates capreomycidine for incorporation into viomycin (tuberactinomycin B). Insertional disruption of the putative hydroxylase gene vioQ resulted in a mutant that accumulated tuberactinomycin O, suggesting that hydroxylation at C-5 of the capreomycidine residue is a post-assembly event. The inactivated chromosomal copy of vioQ could be complemented with a wild-type copy of the gene to restore viomycin production.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2825577 | PMC |
| http://dx.doi.org/10.1021/np060605u | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Mechanistic and Structural Insights into a Divergent PLP-Dependent l-Enduracididine Cyclase from a Toxic Cyanobacterium.
ACS Catal
July 2023
Department of Chemistry and Biochemistry, University of California, Santa Cruz, California 95064, United States.
Cyclic arginine noncanonical amino acids (ncAAs) are found in several actinobacterial peptide natural products with therapeutically useful antibacterial properties. The preparation of ncAAs like enduracididine and capreomycidine currently takes multiple biosynthetic or chemosynthetic steps, thus limiting the commercial availability and applicability of these cyclic guanidine-containing amino acids. We recently discovered and characterized the biosynthetic pathway of guanitoxin, a potent freshwater cyanobacterial neurotoxin, that contains an arginine-derived cyclic guanidine phosphate within its highly polar structure.
View Article and Find Full Text PDFMechanistic and structural insights into a divergent PLP-dependent L-enduracididine cyclase from a toxic cyanobacterium.
bioRxiv
March 2023
Department of Chemistry and Biochemistry, University of California, Santa Cruz, California 95064, United States.
Cyclic arginine noncanonical amino acids (ncAAs) are found in several actinobacterial peptide natural products with therapeutically useful antibacterial properties. The preparation of ncAAs like enduracididine and capreomycidine currently takes multiple biosynthetic or chemosynthetic steps, thus limiting the commercial availability and applicability of these cyclic guanidine-containing amino acids. We recently discovered and characterized the biosynthetic pathway of guanitoxin, a potent freshwater cya-nobacterial neurotoxin, that contains an arginine-derived cyclic guanidine phosphate within its highly polar structure.
View Article and Find Full Text PDFCrystal structure of the α-ketoglutarate-dependent non-heme iron oxygenase CmnC in capreomycin biosynthesis and its engineering to catalyze hydroxylation of the substrate enantiomer.
Front Chem
September 2022
Department of Biological Science and Technology, National Yang Ming Chiao Tung University, Hsinchu, Taiwan.
CmnC is an α-ketoglutarate (α-KG)-dependent non-heme iron oxygenase involved in the formation of the l-capreomycidine (l-Cap) moiety in capreomycin (CMN) biosynthesis. CmnC and its homologues, VioC in viomycin (VIO) biosynthesis and OrfP in streptothricin (STT) biosynthesis, catalyze hydroxylation of l-Arg to form β-hydroxy l-Arg (CmnC and VioC) or β,γ-dihydroxy l-Arg (OrfP). In this study, a combination of biochemical characterization and structural determination was performed to understand the substrate binding environment and substrate specificity of CmnC.
View Article and Find Full Text PDFEnzymatic C-H Functionalization of l-Arg and l-Leu in Nonribosomally Derived Peptidyl Natural Products: A Tale of Two Oxidoreductases.
J Am Chem Soc
November 2021
Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, Kentucky 40536, United States.
Muraymycins are peptidyl nucleoside antibiotics that contain two C-modified amino acids, (2,3)-capreomycidine and (2,3)-β-OH-Leu. The former is also a component of chymostatins, which are aldehyde-containing peptidic protease inhibitors that─like muraymycin─are derived from nonribosomal peptide synthetases (NRPSs). Using feeding experiments and in vitro characterization of 12 recombinant proteins, the biosynthetic mechanism for both nonproteinogenic amino acids is now defined.
View Article and Find Full Text PDFRoles of VioG and VioQ in the incorporation and modification of the Capreomycidine residue in the peptide antibiotic viomycin.
J Nat Prod
April 2007
Program in Molecular and Cellular Biology and Department of Pharmaceutical Sciences, Oregon State University, Corvallis, Oregon 97331-3507, USA.
The nonproteinogenic amino acid capreomycidine is the signature residue found in the tuberactinomycin family of antitubercular peptide antibiotics and an important element of the pharmacophore. Recombinant VioG, a single-module peptide synthetase from the viomycin gene cluster cloned from Streptomyces vinaceus (ATCC11861), specifically activates capreomycidine for incorporation into viomycin (tuberactinomycin B). Insertional disruption of the putative hydroxylase gene vioQ resulted in a mutant that accumulated tuberactinomycin O, suggesting that hydroxylation at C-5 of the capreomycidine residue is a post-assembly event.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!