TY - JOUR
T1 - Conversion of substrate analogs suggests a Michael cyclization in iridoid biosynthesis
AU - Lindner, Stephanie
AU - Geu Flores, Fernando
AU - Bräse, Stefan
AU - Sherden, Nathaniel H
AU - O'Connor, Sarah E
N1 - Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.
PY - 2014/11/20
Y1 - 2014/11/20
N2 - The core structure of the iridoid monoterpenes is formed by a unique cyclization reaction. The enzyme that catalyzes this reaction, iridoid synthase, is mechanistically distinct from other terpene cyclases. Here we describe the synthesis of two substrate analogs to probe the mechanism of iridoid synthase. Enzymatic assay of these substrate analogs along with clues from the product profile of the native substrate strongly suggest that iridoid synthase utilizes a Michael reaction to achieve cyclization. This improved mechanistic understanding will facilitate the exploitation of the potential of iridoid synthase to synthesize new cyclic compounds from nonnatural substrates.
AB - The core structure of the iridoid monoterpenes is formed by a unique cyclization reaction. The enzyme that catalyzes this reaction, iridoid synthase, is mechanistically distinct from other terpene cyclases. Here we describe the synthesis of two substrate analogs to probe the mechanism of iridoid synthase. Enzymatic assay of these substrate analogs along with clues from the product profile of the native substrate strongly suggest that iridoid synthase utilizes a Michael reaction to achieve cyclization. This improved mechanistic understanding will facilitate the exploitation of the potential of iridoid synthase to synthesize new cyclic compounds from nonnatural substrates.
U2 - 10.1016/j.chembiol.2014.09.010
DO - 10.1016/j.chembiol.2014.09.010
M3 - Journal article
C2 - 25444551
SN - 2451-9448
VL - 21
SP - 1452
EP - 1456
JO - Chemistry and Biology
JF - Chemistry and Biology
IS - 11
ER -