Moenomycin Biosynthesis: Structure and Mechanism of Action of the Prenyltransferase MoeN5

Lilan Zhang, Chun Chi Chen, Tzu Ping Ko, Jian Wen Huang, Yingying Zheng, Weidong Liu, Iren Wang, Satish R. Malwal, Xinxin Feng, Ke Wang, Chun Hsiang Huang, Shang Te Danny Hsu, Andrew H.J. Wang, Eric Oldfield, Rey Ting Guo

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)4716-4720
Number of pages5
JournalAngewandte Chemie - International Edition
Issue number15
StatePublished - Apr 4 2016


  • biosynthesis
  • drug discovery
  • enzyme mechanisms
  • isoprenoids
  • protein structure

ASJC Scopus subject areas

  • Catalysis
  • General Chemistry


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