We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Moenomycin Biosynthesis: Structure and Mechanism of Action of the Prenyltransferase MoeN5.
- Authors
Zhang, Lilan; Chen, Chun-Chi; Ko, Tzu-Ping; Huang, Jian-Wen; Zheng, Yingying; Liu, Weidong; Wang, Iren; Malwal, Satish R.; Feng, Xinxin; Wang, Ke; Huang, Chun-Hsiang; Hsu, Shang-Te Danny; Wang, Andrew H.-J.; Oldfield, Eric; Guo, Rey-Ting
- Abstract
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 (C25) 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.
- Subjects
ANTIBIOTIC synthesis; BIOSYNTHESIS; BIOCHEMICAL mechanism of action; DIMETHYLALLYLTRANSTRANSFERASE; ISOPENTENOIDS; DRUG design
- Publication
Angewandte Chemie International Edition, 2016, Vol 55, Issue 15, p4716
- ISSN
1433-7851
- Publication type
Article
- DOI
10.1002/anie.201511388