TY - JOUR
T1 - Context-dependent behavior of the enterocin iterative polyketide synthase
T2 - a new model for ketoreduction
AU - Hertweck, Christian
AU - Xiang, Longkuan
AU - Kalaitzis, John A.
AU - Cheng, Qian
AU - Palzer, Michelle
AU - Moore, Bradley S.
PY - 2004/4
Y1 - 2004/4
N2 - Heterologous expression and mutagenesis of the enterocin type II polyketide synthase (PKS) system suggest for the first time that the association of an extended set of proteins and substrates is needed for the effective production of the enterocin-wailupemycin polyketides. In the absence of its endogenous ketoreductase (KR) EncD in either the enterocin producer "Streptomyces maritimus" or the engineered host S. lividans K4-114, the enterocin minimal PKS is unable to produce benzoate-primed polyketides, even when complemented with the homologous actinorhodin KR ActIII or with EncD active site mutants. These data suggest that the enterocin PKS requires EncD to serve a catalytic and not just a structural role in the functional PKS enzyme complex. This strongly implies that EncD reduces the polyketide chain during elongation rather than after its complete assembly, as suggested for most type II PKSs.
AB - Heterologous expression and mutagenesis of the enterocin type II polyketide synthase (PKS) system suggest for the first time that the association of an extended set of proteins and substrates is needed for the effective production of the enterocin-wailupemycin polyketides. In the absence of its endogenous ketoreductase (KR) EncD in either the enterocin producer "Streptomyces maritimus" or the engineered host S. lividans K4-114, the enterocin minimal PKS is unable to produce benzoate-primed polyketides, even when complemented with the homologous actinorhodin KR ActIII or with EncD active site mutants. These data suggest that the enterocin PKS requires EncD to serve a catalytic and not just a structural role in the functional PKS enzyme complex. This strongly implies that EncD reduces the polyketide chain during elongation rather than after its complete assembly, as suggested for most type II PKSs.
UR - http://www.scopus.com/inward/record.url?scp=1942509576&partnerID=8YFLogxK
U2 - 10.1016/j.chembiol.2004.03.018
DO - 10.1016/j.chembiol.2004.03.018
M3 - Article
C2 - 15123240
AN - SCOPUS:1942509576
SN - 1074-5521
VL - 11
SP - 461
EP - 468
JO - Chemistry and Biology
JF - Chemistry and Biology
IS - 4
ER -