title: Reactivity of the nitrogen-centered tryptophanyl radical in the catalysis by the radical SAM enzyme NosL.
abstract: The radical SAM tryptophan (Trp) lyase NosL involved in nosiheptide biosynthesis catalyzes two parallel reactions, converting l-Trp to 3-methyl-2-indolic acid (MIA) and to dehydroglycine and 3-methylindole, respectively. The two parallel reactions diverge from a nitrogen-centered tryptophanyl radical intermediate. Here we report an investigation on the intrinsic reactivity of the tryptophanyl radical using a chemical model study and DFT calculations. The kinetics of the formation and fragmentation of this nitrogen-centered radical in NosL catalysis were also studied in detail. Our analysis explains the intriguing catalytic promiscuity of NosL and highlights the remarkable role this enzyme plays in achieving an energetically highly unfavorable transformation.
authors.affiliation: College of Life Science, Fujian Agriculture and Forestry University, Fuzhou, 350002, China. jgaotao@gmail.com and Department of Chemistry, Fudan University, Shanghai, 200433, China. qizhang@sioc.ac.cn.
authors.forename: Haocheng
authors.initials: H
authors.lastname: Qianzhu
authors.affiliation: Department of Chemistry, Fudan University, Shanghai, 200433, China. qizhang@sioc.ac.cn.
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Ji
authors.affiliation: Department of Chemistry, Fudan University, Shanghai, 200433, China. qizhang@sioc.ac.cn.
authors.forename: Xinjian
authors.initials: X
authors.lastname: Ji
authors.affiliation: College of Life Science, Fujian Agriculture and Forestry University, Fuzhou, 350002, China. jgaotao@gmail.com.
authors.forename: Leixia
authors.initials: L
authors.lastname: Chu
authors.affiliation: Department of Chemistry, Fudan University, Shanghai, 200433, China. qizhang@sioc.ac.cn.
authors.forename: Chuchu
authors.initials: C
authors.lastname: Guo
authors.affiliation: Department of Chemistry, Fudan University, Shanghai, 200433, China. qizhang@sioc.ac.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Lu
authors.affiliation: Department of Chemistry, Fudan University, Shanghai, 200433, China. qizhang@sioc.ac.cn and School of Life Sciences, Lanzhou University, Lanzhou, 730000, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Ding
authors.affiliation: College of Life Science, Fujian Agriculture and Forestry University, Fuzhou, 350002, China. jgaotao@gmail.com.
authors.forename: Jiangtao
authors.initials: J
authors.lastname: Gao
authors.affiliation: Department of Chemistry, Fudan University, Shanghai, 200433, China. qizhang@sioc.ac.cn.
authors.forename: Qi
authors.identifier: 0000-0002-8135-2221
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D055162:Biocatalysis; D019755:Carbon-Carbon Lyases / Q000378:metabolism*; D005609:Free Radicals / Q000737:chemistry; D007700:Kinetics; D008956:Models, Chemical; D009584:Nitrogen / Q000737:chemistry*; D011789:Quantum Theory; D014364:Tryptophan / Q000737:chemistry*
chemical_list: D005609:Free Radicals; D014364:Tryptophan; D019755:Carbon-Carbon Lyases; D009584:Nitrogen