title: Pictet-Spengler reaction-based biosynthetic machinery in fungi.
abstract: The Pictet-Spengler (PS) reaction constructs plant alkaloids such as morphine and camptothecin, but it has not yet been noticed in the fungal kingdom. Here, a silent fungal Pictet-Spenglerase (FPS) gene of Chaetomium globosum 1C51 residing in Epinephelus drummondhayi guts is described and ascertained to be activable by 1-methyl-L-tryptophan (1-MT). The activated FPS expression enables the PS reaction between 1-MT and flavipin (fungal aldehyde) to form "unnatural" natural products with unprecedented skeletons, of which chaetoglines B and F are potently antibacterial with the latter inhibiting acetylcholinesterase. A gene-implied enzyme inhibition (GIEI) strategy has been introduced to address the key steps for PS product diversifications. In aggregation, the work designs and validates an innovative approach that can activate the PS reaction-based fungal biosynthetic machinery to produce unpredictable compounds of unusual and novel structure valuable for new biology and biomedicine.
authors.affiliation: Institute of Functional Biomolecules, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, China;
authors.forename: Wei
authors.initials: W
authors.lastname: Yan
authors.affiliation: Institute of Functional Biomolecules, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, China;
authors.forename: Hui Ming
authors.initials: HM
authors.lastname: Ge
authors.affiliation: Institute of Functional Biomolecules, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, China; State Key Laboratory of Elemento-organic Chemistry, Nankai University, Tianjin 300071, China;
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Nanjing Medical University, Nanjing 210029, China;
authors.forename: Nan
authors.initials: N
authors.lastname: Jiang
authors.affiliation: Department of Clinical Laboratory, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China;
authors.forename: Ya Ning
authors.initials: YN
authors.lastname: Mei
authors.affiliation: Institute of Functional Biomolecules, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, China;
authors.forename: Rong
authors.initials: R
authors.lastname: Jiang
authors.affiliation: Institute of Functional Biomolecules, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, China;
authors.forename: Sui Jun
authors.initials: SJ
authors.lastname: Li
authors.affiliation: Institute of Functional Biomolecules, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, China;
authors.forename: Chao Jun
authors.initials: CJ
authors.lastname: Chen
authors.affiliation: Institute of Functional Biomolecules, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, China;
authors.forename: Rui Hua
authors.initials: RH
authors.lastname: Jiao
authors.affiliation: Institute of Functional Biomolecules, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, China;
authors.forename: Qiang
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Department of Chemistry, University of Malaya, 50603 Kuala Lumpur, Malaysia; and Chemistry Department, Faculty of Science, King Abdulaziz University, Jeddah 80203, Saudi Arabia.
authors.forename: Seik Weng
authors.initials: SW
authors.lastname: Ng
authors.affiliation: Institute of Functional Biomolecules, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, China; rxtan@nju.edu.cn.
authors.forename: Ren Xiang
authors.initials: RX
authors.lastname: Tan
mesh_terms: D000470:Alkaloids / Q000096:biosynthesis*; D002597:Chaetomium / Q000235:genetics / Q000378:metabolism*; D005800:Genes, Fungal
chemical_list: D000470:Alkaloids
keywords: Chaetomium globosum 1C51; FPS; GIEI; Pictet–Spengler reaction