title: Discovery of a Single Monooxygenase that Catalyzes Carbamate Formation and Ring Contraction in the Biosynthesis of the Legonmycins.
abstract: Pyrrolizidine alkaloids (PAs) are a group of natural products with important biological activities. The discovery and characterization of the multifunctional FAD-dependent enzyme LgnC is now described. The enzyme is shown to convert indolizidine intermediates into pyrrolizidines through an unusual ring expansion/contraction mechanism, and catalyze the biosynthesis of new bacterial PAs, the so-called legonmycins. By genome-driven analysis, heterologous expression, and gene inactivation, the legonmycins were also shown to originate from non-ribosomal peptide synthetases (NRPSs). The biosynthetic origin of bacterial PAs has thus been disclosed for the first time.
authors.affiliation: Key Laboratory of Combinatory Biosynthesis and Drug Discovery (Ministry of Education), School of Pharmaceutical Sciences, Wuhan University, 185 East Lake Road, Wuhan 430071 (P.R. China).
authors.forename: Sheng
authors.initials: S
authors.lastname: Huang
authors.affiliation: Department of Chemistry, University of Aberdeen, Aberdeen (UK).
authors.forename: Jioji
authors.initials: J
authors.lastname: Tabudravu
authors.affiliation: Department of Chemistry, University of Aberdeen, Aberdeen (UK).
authors.forename: Somayah S
authors.initials: SS
authors.lastname: Elsayed
authors.affiliation: Department of Chemistry, University of Aberdeen, Aberdeen (UK).
authors.forename: Jeanne
authors.initials: J
authors.lastname: Travert
authors.affiliation: Department of Chemistry, University of Aberdeen, Aberdeen (UK).
authors.forename: Doe
authors.initials: D
authors.lastname: Peace
authors.affiliation: Department of Chemistry, University of Aberdeen, Aberdeen (UK).
authors.forename: Ming Him
authors.initials: MH
authors.lastname: Tong
authors.affiliation: Department of Chemistry, University of Ghana, P.O. Box LG56, Legon-Accra (Ghana).
authors.forename: Kwaku
authors.initials: K
authors.lastname: Kyeremeh
authors.affiliation: Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, G12 8QQ (UK).
authors.forename: Sharon M
authors.initials: SM
authors.lastname: Kelly
authors.affiliation: Department of Chemistry, University of Aberdeen, Aberdeen (UK).
authors.forename: Laurent
authors.initials: L
authors.lastname: Trembleau
authors.affiliation: Department of Chemistry, University of Aberdeen, Aberdeen (UK).
authors.forename: Rainer
authors.initials: R
authors.lastname: Ebel
authors.affiliation: Department of Chemistry, University of Aberdeen, Aberdeen (UK).
authors.forename: Marcel
authors.initials: M
authors.lastname: Jaspars
authors.affiliation: Key Laboratory of Combinatory Biosynthesis and Drug Discovery (Ministry of Education), School of Pharmaceutical Sciences, Wuhan University, 185 East Lake Road, Wuhan 430071 (P.R. China). yu_yi@whu.edu.cn.
authors.forename: Yi
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Chemistry, University of Aberdeen, Aberdeen (UK). h.deng@abdn.ac.uk.
authors.forename: Hai
authors.initials: H
authors.lastname: Deng
mesh_terms: D001688:Biological Products / Q000737:chemistry / Q000378:metabolism*; D002219:Carbamates / Q000737:chemistry / Q000378:metabolism*; D005798:Genes, Bacterial; D006899:Mixed Function Oxygenases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005810:Multigene Family; D011763:Pyrrolizidine Alkaloids / Q000737:chemistry / Q000378:metabolism*; D012988:Soil Microbiology; D013302:Streptomyces / Q000737:chemistry / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism
chemical_list: D001688:Biological Products; D002219:Carbamates; D011763:Pyrrolizidine Alkaloids; D006899:Mixed Function Oxygenases
keywords: biosynthesis; legonmycins; multifunctional enzymes; non-ribosomal peptide synthetases; pyrrolizidine alkaloids