| Title : Polyketide decarboxylative chain termination preceded by o-sulfonation in curacin a biosynthesis - Gu_2009_J.Am.Chem.Soc_131_16033 |
| Author(s) : Gu L , Wang B , Kulkarni A , Gehret JJ , Lloyd KR , Gerwick L , Gerwick WH , Wipf P , Hakansson K , Smith JL , Sherman DH |
| Ref : Journal of the American Chemical Society , 131 :16033 , 2009 |
| Abstract : Biosynthetic innovation in natural product systems is driven by the recruitment of new genes and enzymes into these complex pathways. Here, an unprecedented decarboxylative chain termination mechanism is described for the polyketide synthase of curacin A, an anticancer lead compound isolated from the marine cyanobacterium Lyngbya majuscula. The unusual chain termination module containing adjacent sulfotransferase (ST) and thioesterase (TE) catalytic domains embedded in CurM was biochemically characterized. The TE was proved to catalyze a hydrolytic chain release of the polyketide chain elongation intermediate. Moreover, a selective ST-mediated sulfonation of the (R)-beta-hydroxyl group was found to precede TE-mediated hydrolysis, triggering a successive decarboxylative elimination and resulting in the formation of a rare terminal olefin in the final metabolite. |
| ESTHER : Gu_2009_J.Am.Chem.Soc_131_16033 |
| PubMedSearch : Gu_2009_J.Am.Chem.Soc_131_16033 |
| PubMedID: 19835378 |
| Gene_locus related to this paper: 9cyan-d0e8e2 |
| Gene_locus related to this paper: 9cyan-d0e8e2 |
Gu L, Wang B, Kulkarni A, Gehret JJ, Lloyd KR, Gerwick L, Gerwick WH, Wipf P, Hakansson K, Smith JL, Sherman DH (2009)
Polyketide decarboxylative chain termination preceded by o-sulfonation in curacin a biosynthesis
Journal of the American Chemical Society
131 :16033
Gu L, Wang B, Kulkarni A, Gehret JJ, Lloyd KR, Gerwick L, Gerwick WH, Wipf P, Hakansson K, Smith JL, Sherman DH (2009)
Journal of the American Chemical Society
131 :16033