title: Moenomycin Biosynthesis: Structure and Mechanism of Action of the Prenyltransferase MoeN5.
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.
authors.affiliation: Industrial Enzymes National Engineering Laboratory, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, 300308, China.
authors.forename: Lilan
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Industrial Enzymes National Engineering Laboratory, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, 300308, China.
authors.forename: Chun-Chi
authors.initials: CC
authors.lastname: Chen
authors.affiliation: Institute of Biological Chemistry, Academia Sinica, Taipei, 11529, Taiwan.
authors.forename: Tzu-Ping
authors.initials: TP
authors.lastname: Ko
authors.affiliation: AsiaPac Biotechnology Co., Ltd., Dongguan, 523808, China.
authors.forename: Jian-Wen
authors.initials: JW
authors.lastname: Huang
authors.affiliation: Industrial Enzymes National Engineering Laboratory, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, 300308, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Industrial Enzymes National Engineering Laboratory, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, 300308, China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Liu
authors.affiliation: Institute of Biological Chemistry, Academia Sinica, Taipei, 11529, Taiwan.
authors.forename: Iren
authors.initials: I
authors.lastname: Wang
authors.affiliation: Department of Chemistry, University of Illinois, Urbana, IL, 61801, USA.
authors.forename: Satish R
authors.initials: SR
authors.lastname: Malwal
authors.affiliation: Department of Chemistry, University of Illinois, Urbana, IL, 61801, USA.
authors.forename: Xinxin
authors.initials: X
authors.lastname: Feng
authors.affiliation: Department of Chemistry, University of Illinois, Urbana, IL, 61801, USA.
authors.forename: Ke
authors.initials: K
authors.lastname: Wang
authors.affiliation: Industrial Enzymes National Engineering Laboratory, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, 300308, China.
authors.forename: Chun-Hsiang
authors.initials: CH
authors.lastname: Huang
authors.affiliation: Institute of Biological Chemistry, Academia Sinica, Taipei, 11529, Taiwan.
authors.forename: Shang-Te Danny
authors.initials: ST
authors.lastname: Hsu
authors.affiliation: Institute of Biological Chemistry, Academia Sinica, Taipei, 11529, Taiwan.
authors.forename: Andrew H-J
authors.initials: AH
authors.lastname: Wang
authors.affiliation: Department of Chemistry, University of Illinois, Urbana, IL, 61801, USA. eo@chad.scs.uiuc.edu.
authors.forename: Eric
authors.initials: E
authors.lastname: Oldfield
authors.affiliation: Industrial Enzymes National Engineering Laboratory, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, 300308, China. guo_rt@tib.cas.cn.
authors.forename: Rey-Ting
authors.initials: RT
authors.lastname: Guo
mesh_terms: D004122:Dimethylallyltranstransferase / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D009844:Oligosaccharides / Q000096:biosynthesis*; D013329:Structure-Activity Relationship
chemical_list: D009844:Oligosaccharides; D004122:Dimethylallyltranstransferase; C419802:moenomycin
keywords: biosynthesis; drug discovery; enzyme mechanisms; isoprenoids; protein structure