Tao Liu, M. Kharel, Lili Zhu
Jan 26, 2009
Citations
1
Influential Citations
30
Citations
Quality indicators
Journal
ChemBioChem
Abstract
Four new analogues of the gilvocarcin‐type aryl‐C‐glycoside antitumor compounds, namely 4′‐hydroxy gilvocarcin V (4′‐OH‐GV), 4′‐hydroxy gilvocarcin M, 4′‐hydroxy gilvocarcin E and 12‐demethyl‐defucogilvocarcin V, were produced through inactivation of the gilU gene. The 4′‐OH‐analogues showed improved activity against lung cancer cell lines as compared to their parent compounds without 4′‐OH group (gilvocarcins V and E). The structures of the sugar‐containing new mutant products indicate that the enzyme GilU acts as an unusual ketoreductase involved in the biosynthesis of the C‐glycosidically linked deoxysugar moiety of the gilvocarcins. The structures of the new gilvocarcins indicate substrate flexibility of the post‐polyketide synthase modifying enzymes, particularly the C‐glycosyltransferase and the enzyme responsible for the sugar ring contraction. The results also shed light into biosynthetic sequence of events in the late steps of biosynthetic pathway of gilvocarcin V.