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

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