Departamento de Biología Funcional e Instituto Universitario de Oncología del Principado de Asturias (I.U.O.P.A.), Universidad de Oviedo, Oviedo 33006, Spain.
Bioorg Med Chem Lett. 2013 Oct 15;23(20):5707-9. doi: 10.1016/j.bmcl.2013.08.017. Epub 2013 Aug 12.
Collismycin A is a member of the 2,2'-bipyridyl family of natural products and structurally belongs to the hybrid polyketides-nonribosomal peptides. A gene coding for a lysine 2-aminotransferase of Streptomyces sp. CS40 (collismycin A producer) was inactivated by gene replacement. The mutant was unable of synthesizing collismycin A but it recovered this capability when picolinic acid was added to the culture medium. By feeding different picolinic acid analogs to this mutant, two new collismycin A derivatives were obtained with a methyl group at the 4 and 6 position of the first pyridine ring of collismycin A, respectively. The two compounds showed effective neuroprotective action against an oxidative stress inducer in a zebra fish model, one of them showing higher neuroprotectant activity than that of collismycin A and that of the control lipoic acid.
卷曲霉素 A 是 2,2'-联吡啶类天然产物的一个成员，在结构上属于杂合聚酮-非核糖体肽。通过基因替换使产生卷曲霉素 A 的链霉菌 CS40 中的赖氨酸 2-氨基转移酶基因失活。该突变体无法合成卷曲霉素 A，但当在培养基中添加吡啶酸时，它恢复了这种能力。通过向该突变体饲喂不同的吡啶酸类似物，获得了两个新的卷曲霉素 A 衍生物，它们在卷曲霉素 A 的第一个吡啶环的 4 和 6 位分别具有一个甲基。这两种化合物在斑马鱼模型中对氧化应激诱导物表现出有效的神经保护作用，其中一种化合物的神经保护活性高于卷曲霉素 A 和对照物硫辛酸。
