Discovery of a Single Monooxygenase that Catalyzes Carbamate Formation and Ring Contraction in the Biosynthesis of the Legonmycins
Sheng Huang
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)
These authors contributed equally to this work.
Search for more papers by this authorDr. Jioji Tabudravu
Department of Chemistry, University of Aberdeen, Aberdeen (UK)
These authors contributed equally to this work.
Search for more papers by this authorSomayah S. Elsayed
Department of Chemistry, University of Aberdeen, Aberdeen (UK)
These authors contributed equally to this work.
Search for more papers by this authorJeanne Travert
Department of Chemistry, University of Aberdeen, Aberdeen (UK)
Search for more papers by this authorDoe Peace
Department of Chemistry, University of Aberdeen, Aberdeen (UK)
Search for more papers by this authorMing Him Tong
Department of Chemistry, University of Aberdeen, Aberdeen (UK)
Search for more papers by this authorDr. Kwaku Kyeremeh
Department of Chemistry, University of Ghana, P.O. Box LG56, Legon-Accra (Ghana)
Search for more papers by this authorDr. Sharon M. Kelly
Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, G12 8QQ (UK)
Search for more papers by this authorDr. Laurent Trembleau
Department of Chemistry, University of Aberdeen, Aberdeen (UK)
Search for more papers by this authorDr. Rainer Ebel
Department of Chemistry, University of Aberdeen, Aberdeen (UK)
Search for more papers by this authorProf. Dr. Marcel Jaspars
Department of Chemistry, University of Aberdeen, Aberdeen (UK)
Search for more papers by this authorCorresponding Author
Dr. Yi Yu
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)
Yi Yu, 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)
Hai Deng, Department of Chemistry, University of Aberdeen, Aberdeen (UK)
Search for more papers by this authorCorresponding Author
Dr. Hai Deng
Department of Chemistry, University of Aberdeen, Aberdeen (UK)
Yi Yu, 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)
Hai Deng, Department of Chemistry, University of Aberdeen, Aberdeen (UK)
Search for more papers by this authorSheng Huang
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)
These authors contributed equally to this work.
Search for more papers by this authorDr. Jioji Tabudravu
Department of Chemistry, University of Aberdeen, Aberdeen (UK)
These authors contributed equally to this work.
Search for more papers by this authorSomayah S. Elsayed
Department of Chemistry, University of Aberdeen, Aberdeen (UK)
These authors contributed equally to this work.
Search for more papers by this authorJeanne Travert
Department of Chemistry, University of Aberdeen, Aberdeen (UK)
Search for more papers by this authorDoe Peace
Department of Chemistry, University of Aberdeen, Aberdeen (UK)
Search for more papers by this authorMing Him Tong
Department of Chemistry, University of Aberdeen, Aberdeen (UK)
Search for more papers by this authorDr. Kwaku Kyeremeh
Department of Chemistry, University of Ghana, P.O. Box LG56, Legon-Accra (Ghana)
Search for more papers by this authorDr. Sharon M. Kelly
Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, G12 8QQ (UK)
Search for more papers by this authorDr. Laurent Trembleau
Department of Chemistry, University of Aberdeen, Aberdeen (UK)
Search for more papers by this authorDr. Rainer Ebel
Department of Chemistry, University of Aberdeen, Aberdeen (UK)
Search for more papers by this authorProf. Dr. Marcel Jaspars
Department of Chemistry, University of Aberdeen, Aberdeen (UK)
Search for more papers by this authorCorresponding Author
Dr. Yi Yu
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)
Yi Yu, 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)
Hai Deng, Department of Chemistry, University of Aberdeen, Aberdeen (UK)
Search for more papers by this authorCorresponding Author
Dr. Hai Deng
Department of Chemistry, University of Aberdeen, Aberdeen (UK)
Yi Yu, 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)
Hai Deng, Department of Chemistry, University of Aberdeen, Aberdeen (UK)
Search for more papers by this authorAbstract
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.
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