Abstract：
:The streptothricin (ST) antibiotics, produced by Streptomyces bacteria, contain L-β-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-β-lysine by ORF 5, followed by transfer to the T domain of ORF 18. In contrast, L-β-lysine molecules adenylated by ORF 19 are used to elongate an L-β-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-β-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.
journal_name
Nat Chem Bioljournal_title
Nature chemical biologyauthors
Maruyama C,Toyoda J,Kato Y,Izumikawa M,Takagi M,Shin-ya K,Katano H,Utagawa T,Hamano Ydoi
10.1038/nchembio.1040subject
Has Abstractpub_date
2012-09-01 00:00:00pages
791-7issue
9eissn
1552-4450issn
1552-4469pii
nchembio.1040journal_volume
8pub_type
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