title: OxaD: A Versatile Indolic Nitrone Synthase from the Marine-Derived Fungus Penicillium oxalicum F30.
abstract: Indole alkaloids are a diverse class of natural products known for their wide range of biological activities and complex chemical structures. Rarely observed in this class are indolic nitrones, such as avrainvillamide and waikialoid, which possess potent bioactivities. Herein the oxa gene cluster from the marine-derived fungus Penicillium oxalicum F30 is described along with the characterization of OxaD, a flavin-dependent oxidase that generates roquefortine L, a nitrone-bearing intermediate in the biosynthesis of oxaline. Nitrone functionality in roquefortine L was confirmed by spectroscopic methods and 1,3-dipolar cycloaddition with methyl acrylate. OxaD is a versatile biocatalyst that converts an array of semisynthetic roquefortine C derivatives bearing indoline systems to their respective nitrones. This work describes the first implementation of a nitrone synthase as a biocatalyst and establishes a novel platform for late-stage diversification of a range of complex natural products.
authors: Sean A
authors: SA
authors: Newmister
authors: Department of Chemistry, University of Pennsylvania , 231 South 34th Street, Philadelphia, Pennsylvania 19104, United States.
authors: Claire M
authors: CM
authors: Gober
authors: Stelamar
authors: S
authors: Romminger
authors: Fengan
authors: F
authors: Yu
authors: Ashootosh
authors: A
authors: Tripathi
authors: Instituto de Química de São Carlos, Universidade de São Paulo , CP 780, São Carlos, São Paulo CEP 13560-970, Brazil.
authors: Lizbeth Lorena L
authors: LL
authors: Parra
authors: Department of Chemistry, Colorado State University , Fort Collins, Colorado 80523, United States.|University of Colorado Cancer Center , Aurora, Colorado 80045, United States.
authors: Robert M
authors: RM
authors: Williams
authors: Instituto de Química de São Carlos, Universidade de São Paulo , CP 780, São Carlos, São Paulo CEP 13560-970, Brazil.
authors: Roberto G S
authors: RG
authors: Berlinck
authors: Department of Chemistry, University of Pennsylvania , 231 South 34th Street, Philadelphia, Pennsylvania 19104, United States.
authors: Madeleine M
authors: MM
authors: Joullié
authors: David H
authors: DH
authors: Sherman
mesh_terms: D055162:Biocatalysis; D006576:Heterocyclic Compounds, 4 or More Rings / Q000378:metabolism; D007093:Imidazoles / Q000378:metabolism; D007211:Indoles / Q000737:chemistry* / Q000378:metabolism; D005810:Multigene Family / Q000235:genetics; D009589:Nitrogen Oxides / Q000737:chemistry* / Q000378:metabolism*; D010084:Oxidation-Reduction; D010105:Oxygenases / Q000378:metabolism*; D010407:Penicillium / Q000201:enzymology* / Q000235:genetics; D010879:Piperazines / Q000378:metabolism
chemical_list: D006576:Heterocyclic Compounds, 4 or More Rings; D007093:Imidazoles; D007211:Indoles; D009589:Nitrogen Oxides; D010879:Piperazines; C015388:nitrones; C490207:oxaline; C012536:roquefortine; D010105:Oxygenases