Hybrid compounds derived from the combination of anthracycline and actinorhodin biosynthetic pathways

Abstract

A new approach in the field of polyketide biosynthetic engineering, the combination of the biosynthetic routes of two different sources, is introduced. Streptomyces nogalater genes expressed in S. lividans TK24 yield the hybrid strain TK24/pSY15. Structural analysis of the products isolated from cultivation of the hybrid strain revealed the ability of the hybrid to produce novel compounds. Instead of accumulating characteristic products (e.g. actinorhodin) of the host S. lividans TK24, or intermediate compounds expected to be generated by the plasmid pSY15 (e.g. nogalamycin precursor), the hybrid strain produces novel compounds reflecting the enzymatic activity of both the host and the expressed plasmid. This implies that genes from two different types of aromatic polyketide biosynthesis are working together. The method described in this work complements earlier targeted biosyntheses.