Garcia Ignacio, Vior Natalia M, Braña Alfredo F, González-Sabin Javier, Rohr Jürgen, Moris Francisco, Méndez Carmen, Salas José A
Departamento de Biología Funcional e Instituto Universitario de Oncología del Principado de Asturias-I.U.O.P.A, Universidad de Oviedo, 33006 Oviedo, Spain.
Chem Biol. 2012 Mar 23;19(3):399-413. doi: 10.1016/j.chembiol.2012.01.014.
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.
从链霉菌属CS40中鉴定出了双吡啶化合物可利霉素的基因簇。对一个46.7 kb的DNA区域进行序列分析，发现了27个开放阅读框，其中23个参与可利霉素的生物合成。在测序区域产生了8个插入失活突变体，以证明其参与可利霉素的生物合成，确定该基因簇的边界，对一些基因进行功能表征，并分离出两种生物合成中间体。提出了一个可利霉素生物合成模型，该模型包括赖氨酸转化为吡啶甲酸、聚酮合酶-非核糖体肽合成酶系统的参与以及一些进一步的修饰。生物合成途径将包括一个由非核糖体肽合成酶介导的不寻常的半胱氨酸残基掺入，可能是通过迈克尔加成，随后通过亮氨酸掺入延伸肽链，最后由酰胺水解酶去除。
