Landomycin biosynthesis and its regulation in Streptomyces

Abstract

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.

Keywords: Angucyclines; Antibiotic export; Biosynthesis; Landomycins; Regulation.