Inactivation of the carbamoyltransferase gene refines post-polyketide synthase modification steps in the biosynthesis of the antitumor agent geldanamycin

Geldanamycin (1) and its closely related analogues, herbimycin B (6) and macbecin are naturally occurring antitumor antibiotics. Geldanamycin binds to the N-terminal ATP binding site of heat shock protein (Hsp) 90 inhibiting its chaperone activity.