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A stand-alone adenylation domain forms amide bonds in streptothricin biosynthesis.
- Source :
-
Nature Chemical Biology . Sep2012, Vol. 8 Issue 9, p791-797. 7p. 2 Diagrams, 3 Graphs. - Publication Year :
- 2012
-
Abstract
- The streptothricin (ST) antibiotics, produced by Streptomyces bacteria, contain L-?-lysine ((3S)-3,6-diaminohexanoic acid) oligopeptides as pendant chains. Here we describe three unusual nonribosomal peptide synthetases (NRPSs) involved in ST biosynthesis: ORF 5 (a stand-alone adenylation (A) domain), ORF 18 (containing thiolation (T) and condensation (C) domains) and ORF 19 (a stand-alone A domain). We demonstrate that ST biosynthesis begins with adenylation of L-?-lysine by ORF 5, followed by transfer to the T domain of ORF 18. In contrast, L-?-lysine molecules adenylated by ORF 19 are used to elongate an L-?-lysine peptide chain on ORF 18, a reaction unexpectedly catalyzed by ORF 19 itself. Finally, the C domain of ORF 18 catalyzes the condensation of L-?-lysine oligopeptides covalently bound to ORF 18 with a freely diffusible intermediate to release the ST products. These results highlight an unusual activity for an A domain and unique mechanisms of crosstalk within NRPS machinery. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 15524450
- Volume :
- 8
- Issue :
- 9
- Database :
- Academic Search Index
- Journal :
- Nature Chemical Biology
- Publication Type :
- Academic Journal
- Accession number :
- 79291600
- Full Text :
- https://doi.org/10.1038/nchembio.1040