期刊
CHEMISTRY & BIOLOGY
卷 19, 期 3, 页码 399-413出版社
CELL PRESS
DOI: 10.1016/j.chembiol.2012.01.014
关键词
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资金
- Spanish Ministry of Science and Innovation [BIO2009-07643]
- Red Tematica de Investigacion Cooperativa de Centros de Cancer (Ministry of Health) [ISCIII-RETIC RD06/0020/0026]
The gene cluster for the bipyridyl compound collismycin was characterized from Streptomyces sp. CS40. Sequence analysis of a 46.7 kb DNA region revealed 27 open reading frames, 23 of which are involved in collismycin biosynthesis. Eight insertional inactivation mutants were generated in the sequenced region to prove its involvement in collismycin biosynthesis, define the boundaries of the cluster, functionally characterize some genes, and isolate two biosynthetic intermediates. A model for collismycin biosynthesis-which includes the conversion of lysine into picolinic acid, participation of a polyketide synthase-non-ribosomal peptide synthetase system, and some further modifications is proposed. The biosynthetic pathway would include an unusual NRPS-mediated incorporation of a cysteine residue, possibly through a Michael addition and followed by the extension of the peptide chain by leucine incorporation and later removal by amidohydrolase.
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