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β‐Amyrin Biosynthesis: The Methyl‐30 Group of (3 S )‐2,3‐Oxidosqualene Is More Critical to Its Correct Folding To Generate the Pentacyclic Scaffold than the Methyl‐24 Group
Author(s) -
Hoshino Tsutomu,
Miyahara Yuri,
Hanaoka Masaki,
Takahashi Kazunari,
Kaneko Ikki
Publication year - 2015
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201502389
Subject(s) - folding (dsp implementation) , group (periodic table) , biosynthesis , scaffold , stereochemistry , chemistry , computer science , biochemistry , engineering , structural engineering , gene , organic chemistry , database
Oxidosqualene cyclases catalyze the transformation of oxidosqualene ( 1 ) into numerous cyclic triterpenes. Enzymatic reactions of 24‐noroxidosqualene ( 8 ) and 30‐noroxidosqualene ( 9 ) with Euphorbia tirucalli β‐amyrin synthase were conducted to examine the role of the branched methyl groups of compound 1 in the β‐amyrin biosynthesis. Substrate 8 almost exclusively afforded 30‐nor‐β‐amyrin (>95.5 %), which was produced through a normal cyclization pathway, along with minor products (<4.5 %). However, a lack of the Me‐30 group (analogue 9 ) resulted in significantly high production of premature cyclization products, including 6/6/6/5‐fused tetracyclic and 6/6/6/6/5‐fused pentacyclic skeletons (64.6 %). In addition, the fully cyclized product (35.4 %) having the 6/6/6/6/6‐fused pentacycle was produced; however, the normally cyclized product, 29‐nor‐β‐amyrin was present in only 18.6 % of these products. The conversion yield of substrate 8 possessing a Z ‐Me group at the terminus was approximately twofold greater than that of compound 9 with an E ‐Me group. Thus, the Me‐30 group is essential for the correct folding of a chair–chair–chair–boat–boat conformation of compound 1 for the production of the β‐amyrin scaffold, whereas the Me‐24 group exerts little influence on the normal polycyclization cascade. Here, we show that the Me‐30 group plays critical roles in constructing the ordered architecture of a chair–chair–chair–boat–boat structure, in facilitating the ring‐expansion reactions, and in performing the final deprotonation reaction at the correct position.