New, Highly Active Nonbenzoquinone Geldanamycin Derivatives by Using Mutasynthesis

You are what you eat: The feeding of aromatic and heteroaromatic amino acids to an AHBA-blocked mutant of S. hygroscopicus yielded new analogues of the highly potent Hsp90 inhibitor geldanamycin. Except for a “pyridine”-geldanamycin derivative, all new compounds had strong antiproliferative activity (IC50 values in the nM range).