title: Biosynthetic investigation of phomopsins reveals a widespread pathway for ribosomal natural products in Ascomycetes.
abstract: Production of ribosomally synthesized and posttranslationally modified peptides (RiPPs) has rarely been reported in fungi, even though organisms of this kingdom have a long history as a prolific source of natural products. Here we report an investigation of the phomopsins, antimitotic mycotoxins. We show that phomopsin is a fungal RiPP and demonstrate the widespread presence of a pathway for the biosynthesis of a family of fungal cyclic RiPPs, which we term dikaritins. We characterize PhomM as an S-adenosylmethionine-dependent α-N-methyltransferase that converts phomopsin A to an N,N-dimethylated congener (phomopsin E), and show that the methyltransferases involved in dikaritin biosynthesis have evolved differently and likely have broad substrate specificities. Genome mining studies identified eight previously unknown dikaritins in different strains, highlighting the untapped capacity of RiPP biosynthesis in fungi and setting the stage for investigating the biological activities and unknown biosynthetic transformations of this family of fungal natural products.
authors.affiliation: Department of Chemistry, Fudan University, Shanghai 200433, China;
authors.forename: Wei
authors.initials: W
authors.lastname: Ding
authors.affiliation: Department of Chemistry, Fudan University, Shanghai 200433, China;
authors.forename: Wan-Qiu
authors.initials: WQ
authors.lastname: Liu
authors.affiliation: Department of Chemistry, Fudan University, Shanghai 200433, China;
authors.forename: Youli
authors.initials: Y
authors.lastname: Jia
authors.affiliation: Department of Chemistry, Fudan University, Shanghai 200433, China;
authors.forename: Yongzhen
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801; Howard Hughes Medical Institute, University of Illinois at Urbana-Champaign, Urbana, IL 61801 vddonk@illinois.edu qizhang@sioc.ac.cn.
authors.forename: Wilfred A
authors.initials: WA
authors.lastname: van der Donk
authors.affiliation: Department of Chemistry, Fudan University, Shanghai 200433, China; Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801; vddonk@illinois.edu qizhang@sioc.ac.cn.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D000595:Amino Acid Sequence; D050256:Antimitotic Agents / Q000737:chemistry / Q000378:metabolism; D001203:Ascomycota / Q000235:genetics / Q000378:metabolism*; D001688:Biological Products / Q000737:chemistry / Q000378:metabolism; D053898:Biosynthetic Pathways; D005656:Fungal Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics; D005800:Genes, Fungal; D008969:Molecular Sequence Data; D005810:Multigene Family; D009183:Mycotoxins / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D011496:Protein Methyltransferases / Q000235:genetics / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D020449:Repetitive Sequences, Amino Acid; D012270:Ribosomes / Q000378:metabolism; D009842:Oligopeptides
chemical_list: D050256:Antimitotic Agents; D001688:Biological Products; D005656:Fungal Proteins; D009183:Mycotoxins; D011496:Protein Methyltransferases; C035753:phomopsin; D009842:Oligopeptides
keywords: RiPP; biosynthesis; methyltransferase; mycotoxin; posttranslational modification