Identification of 4,5-Dihydro-4-hydroxygeldanamycins As Shunt Products of Geldanamycin Biosynthesis

Two new geldanamycin (GDM) analogues, (4<i>S</i>)-4,5-dihydro-4-hydroxygeldanamycin (<b>1</b>) and (4<i>R</i>)-4,5-dihydro-4-hydroxygeldanamycin (<b>2</b>), were identified from <i>Streptomyces hygroscopicus</i> 17997. Compounds <b>1</b> and <b>2</b> were not normal intermediates of GDM biosynthesis but shunt products of C-4,5 oxidation catalyzed by GdmP, a cytochrome P450 oxidase acting as a desaturase in GDM biosynthesis. Preliminary assays implied that, compared with GDM, <b>1</b> and <b>2</b> exhibited decreased cytotoxicity.