Department of Genetics and Biotechnology, Ivan Franko National University of Lviv, Hrushevskoho St. 4, Rm. 102, Lviv, 79005, Ukraine.
Department of Pharmaceutical Sciences, University of Maryland Eastern Shore, Somerset Hall 214, Princess Anne, MD, 21853, USA.
Appl Microbiol Biotechnol. 2019 Feb;103(4):1659-1665. doi: 10.1007/s00253-018-09601-1. Epub 2019 Jan 11.
This mini-review is centered on genetic aspects of biosynthesis of landomycins (La), a family of angucycline polyketides. From the very discovery in the 1990s, La were noted for unusual structure and potent anticancer properties. La are produced by a few actinobacteria that belong to genus Streptomyces. Biochemical logic behind the production of La aglycon and glycoside halves and effects of La on mammalian cells have been thoroughly reviewed in 2009-2012. Yet, the genetic diversity of La biosynthetic gene clusters (BGCs) and regulation of their production were not properly reviewed since discovery of La. Here, we aim to fill this gap by focusing on three interrelated topics. First, organization of known La BGCs is compared. Second, up-to-date scheme of biosynthetic pathway to landomycin A (LaA), the biggest (by molar weight) member of La family, is succinctly outlined. Third, we describe genetic and nutritional factors that influence La production and export. A summary of the practical utility of the gained knowledge and future directions to study La biosynthesis conclude this mini-review.
这篇小型综述主要集中在土地霉素(La)生物合成的遗传方面,土地霉素是一种蒽环类聚酮化合物家族。从 20 世纪 90 年代首次发现以来,La 因其独特的结构和强大的抗癌特性而备受关注。La 由少数属于链霉菌属的放线菌产生。2009 年至 2012 年,人们对 La 苷元和糖苷半部分的生物合成以及 La 对哺乳动物细胞的影响的生化逻辑进行了全面综述。然而,自 La 发现以来,其生物合成基因簇(BGCs)的遗传多样性和生产调控尚未得到适当的综述。在这里,我们旨在通过关注三个相互关联的主题来填补这一空白。首先,比较了已知 La BGCs 的组织。其次,简要概述了土地霉素 A(LaA)生物合成途径的最新方案,LaA 是 La 家族中分子量最大的成员。第三,我们描述了影响 La 生产和出口的遗传和营养因素。本小型综述总结了所获得知识的实际应用和研究 La 生物合成的未来方向。