Fig. 9. Diversification of geldanamycin achieved via DH engineering and disruption of post-PKS processing. (A) Geldanamycin and (B) novel analogue DHQ3 generated by DH domain inactivation and gene disruption of an oxidative tailoring enzyme responsible for formation of the quinone ring. In addition to retaining the expected hydroxylation at C15 and lacking quinone functionality, DHQ3 also lacks O-methylation of the aromatic ring moiety and an alkene group on the polyketide backbone, both of which are installed during post-PKS tailoring steps.
