title: A ThDP-dependent enzymatic carboligation reaction involved in Neocarazostatin A tricyclic carbazole formation.
abstract: Although the biosynthetic pathway of Neocarazostatin A (1) has been identified, the detailed enzymatic reactions underlying the assembly of the carbazole ring still remain largely unknown. We demonstrate here that NzsH, a putative thiamine diphosphate dependent enzyme, can catalyze an acyloin coupling reaction between indole-3-pyruvate and pyruvate to generate a β-ketoacid intermediate. Our findings thus shed light on further characterization of the unusual biosynthetic pathway of the bacterial tricyclic carbazole alkaloids.
authors.affiliation: Key Laboratory of Combinatorial 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: Li
authors.initials: L
authors.lastname: Su
authors.affiliation: Key Laboratory of Combinatorial 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: Meinan
authors.initials: M
authors.lastname: Lv
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: Key Laboratory of Combinatorial 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: Zixin
authors.initials: Z
authors.lastname: Deng
authors.affiliation: Marine Biodiscovery Centre, Department of Chemistry, University of Aberdeen, Aberdeen AB24 3UE, Scotland, UK.
authors.forename: Hai
authors.initials: H
authors.lastname: Deng
authors.affiliation: Key Laboratory of Combinatorial 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
mesh_terms: D053898:Biosynthetic Pathways; D002227:Carbazoles / Q000378:metabolism*; D005798:Genes, Bacterial; D007211:Indoles / Q000378:metabolism; D007700:Kinetics; D005810:Multigene Family; D010802:Phylogeny; D019289:Pyruvic Acid / Q000378:metabolism; D013302:Streptomyces / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D013835:Thiamine Pyrophosphate / Q000378:metabolism*
chemical_list: D002227:Carbazoles; D007211:Indoles; C071015:neocarazostatin A; C008122:indol-3-yl pyruvic acid; D019289:Pyruvic Acid; D013835:Thiamine Pyrophosphate