TY - JOUR
T1 - Chemoenzymatic synthesis of the polyketide macrolactone 10-deoxymethynolide
AU - Aldrich, Courtney C.
AU - Venkatraman, Lakshmanan
AU - Sherman, David H.
AU - Fecik, Robert A.
PY - 2005/6/29
Y1 - 2005/6/29
N2 - The polyketide synthase-derived pikromycin thioesterase (Pik TE) is unique in its ability to catalyze the cyclization of 12- and 14-membered macrolactones. In this investigation, the total synthesis of the natural hexaketide chain elongation intermediate as its N-acetyl cysteamine (NAC) thioester has been achieved, and its reaction with Pik TE demonstrated the ability of Pik TE to catalyze its macrolactonization to the natural product 10-deoxymethynolide. A steady-state kinetic analysis of the hexaketide chain intermediate with Pik TE was done. A preliminary substrate specificity study with unnatural hexaketide analogues was accomplished, demonstrating the importance of total synthesis in obtaining access to advanced polyketide intermediates. The results show the sensitivity of Pik TE to minor substrate modifications, and illustrate the potential use of thioesterases as versatile macrolactonization catalysts.
AB - The polyketide synthase-derived pikromycin thioesterase (Pik TE) is unique in its ability to catalyze the cyclization of 12- and 14-membered macrolactones. In this investigation, the total synthesis of the natural hexaketide chain elongation intermediate as its N-acetyl cysteamine (NAC) thioester has been achieved, and its reaction with Pik TE demonstrated the ability of Pik TE to catalyze its macrolactonization to the natural product 10-deoxymethynolide. A steady-state kinetic analysis of the hexaketide chain intermediate with Pik TE was done. A preliminary substrate specificity study with unnatural hexaketide analogues was accomplished, demonstrating the importance of total synthesis in obtaining access to advanced polyketide intermediates. The results show the sensitivity of Pik TE to minor substrate modifications, and illustrate the potential use of thioesterases as versatile macrolactonization catalysts.
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U2 - 10.1021/ja0504340
DO - 10.1021/ja0504340
M3 - Article
C2 - 15969542
AN - SCOPUS:21244484972
SN - 0002-7863
VL - 127
SP - 8910
EP - 8911
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
IS - 25
ER -