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Moenomycin Biosynthesis: Structure and Mechanism of Action of the Prenyltransferase MoeN5
Author(s) -
Zhang Lilan,
Chen ChunChi,
Ko TzuPing,
Huang JianWen,
Zheng Yingying,
Liu Weidong,
Wang Iren,
Malwal Satish R.,
Feng Xinxin,
Wang Ke,
Huang ChunHsiang,
Hsu ShangTe Danny,
Wang Andrew H.J.,
Oldfield Eric,
Guo ReyTing
Publication year - 2016
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201511388
Subject(s) - prenyltransferase , allylic rearrangement , stereochemistry , chemistry , biosynthesis , glycolipid , mechanism of action , enzyme , biochemistry , catalysis , in vitro
The structure of MoeN5, a unique prenyltransferase involved in the biosynthesis of the antibiotic moenomycin, is reported. MoeN5 catalyzes the reaction of geranyl diphosphate (GPP) with the cis ‐farnesyl group in phosphoglycolipid 5 to form the (C 25 ) moenocinyl‐sidechain‐containing lipid 7 . GPP binds to an allylic site (S1) and aligns well with known S1 inhibitors. Alkyl glycosides, glycolipids, can bind to both S1 and a second site, S2. Long sidechains in S2 are “bent” and co‐locate with the homoallylic substrate isopentenyl diphosphate in other prenyltransferases. These observations support a MoeN5 mechanism in which 5 binds to S2 with its C6–C11 group poised to attack C1 in GPP to form the moenocinyl sidechain, with the more distal regions of 5 aligning with the distal glucose in decyl maltoside. The results are of general interest because they provide the first structures of MoeN5 and a structural basis for its mechanism of action, results that will facilitate the design of new antibiotics.