Regiospecific Synthesis of Polyketide Natural Products Using Polyketide Synthase Shiou-chuan (Sheryl) Tsai, Department of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697-3900 O
O
14 O
O
O
tcmARO O
O
OH O
OH O
O O
14
OH O
OH
COOH tcmI
COOH
O
9
S-ACP
HO
9
OH
HO
OH
TcmF2
TcmF1
C9-C14
OH O
14
HO
WT
O
9
O O
N136A
OH
E34A Y35
R69
Y35T OH O
R69A standard
OH
12
C7-C12
HO
OH
7 O HO
O
Structure-based mutation changed cyclization outcome from C9-C14 to C7-C12, as well as the chain length of polyketides, for the regio-specific production of “unnatural” natural product