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- 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; BIOCHEMICAL mechanism of action; BIOSYNTHESIS; DIMETHYLALLYLTRANSTRANSFERASE; ANTIBIOTICS manufacturing
- Publication
Angewandte Chemie, 2016, Vol 128, Issue 15, p4794
- ISSN
0044-8249
- Publication type
Article
- DOI
10.1002/ange.201511388