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Deciphering the biosynthetic codes for the potent anti-SARS-CoV cyclodepsipeptide valinomycin in Streptomyces tsusimaensis ATCC 15141.
- Source :
-
Chembiochem : a European journal of chemical biology [Chembiochem] 2006 Mar; Vol. 7 (3), pp. 471-7. - Publication Year :
- 2006
-
Abstract
- Valinomycin was recently reported to be the most potent agent against severe acute respiratory-syndrome coronavirus (SARS-CoV) in infected Vero E6 cells. Aimed at generating analogues by metabolic engineering, the valinomycin biosynthetic gene cluster has been cloned from Streptomyces tsusimaensis ATCC 15141. Targeted disruption of a nonribosomal peptide synthetase (NRPS) gene abolishes valinomycin production, which confirms its predicted nonribosomal-peptide origin. Sequence analysis of the NRPS system reveals four distinctive modules, two of which contain unusual domain organizations that are presumably involved in the generation of biosynthetic precursors D-alpha-hydroxyisovaleric acid and L-lactic acid. The respective adenylation domains in these two modules contain novel substrate-specificity-conferring codes that might specify for a class of hydroxyl acids for the biosynthesis of the depsipeptide natural products.
- Subjects :
- Animals
Antiviral Agents pharmacology
Chlorocebus aethiops
Genes, Bacterial
Molecular Sequence Data
Multigene Family
Streptomyces genetics
Vero Cells
Anti-Bacterial Agents biosynthesis
Antiviral Agents metabolism
Severe acute respiratory syndrome-related coronavirus drug effects
Streptomyces metabolism
Valinomycin biosynthesis
Subjects
Details
- Language :
- English
- ISSN :
- 1439-4227
- Volume :
- 7
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Chembiochem : a European journal of chemical biology
- Publication Type :
- Academic Journal
- Accession number :
- 16511823
- Full Text :
- https://doi.org/10.1002/cbic.200500425