1. Engineered Biosynthesis of Geldanamycin Analogs for Hsp90 Inhibition
Kedar Patel, Misty Piagentini, Andreas Rascher, Zong-Qiang Tian, Greg O. Buchanan, Rika Regentin, Zhihao Hu, C.R. Hutchinson, Robert McDaniel 
Chemistry & Biology 
Volume 11, Issue 12, Pages (December 2004)
DOI: /j.chembiol
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2. Figure 1 Geldanamycin, 17-AAG, and Related Ansamycin Polyketides
Chemistry & Biology  , DOI: ( /j.chembiol )
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3. Figure 2 Genetics and Chemistry of Geldanamycin Biosynthesis
Progeldanamycin is the presumed polyketide product of the GdmPKS (encoded by gdmA1, A2, and A3) and GdmF (the lactam-forming amide synthase). The GdmPKS consists of an AHBA loading domain and seven extension modules. Each module catalyzes one round of chain elongation using malonyl-CoA (module 6), methylmalonyl-CoA (modules 1, 3, 5, and 7), or methoxymalonyl-ACP (modules 2 and 6). Each module also modifies the β-carbonyl from each elongation to a hydroxyl (modules 3 and 5), alkene (modules 4 and 7), or methylene (modules 1, 2, and 6). Progeldanamycin is converted to geldanamycin by five steps, the precise order of which has not been determined. (KS-ketosynthase, AT-acyltransferase, DH-dehydratase, ER-enolreductase, KR-ketoreductase, ACP-acyl carrier protein).
Chemistry & Biology  , DOI: ( /j.chembiol )
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4. Figure 3 Junctions Used for AT Domain Substitutions
Green sequences correspond to geldanamycin flanking regions, blue to rapamycin ATs, and red to amino acids introduced by restriction site engineering.
Chemistry & Biology  , DOI: ( /j.chembiol )
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5. Figure 4
Geldanamycin Analogs Produced by AT Substitutions in the GdmPKS
Chemistry & Biology  , DOI: ( /j.chembiol )
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