title: A mutasynthesis approach with a Penicillium chrysogenum ΔroqA strain yields new roquefortine D analogues.
abstract: Penicillium chrysogenum, which lacks the roqA gene, processes synthetic, exogenously added histidyltryptophanyldiketopiperazine (HTD) to yield a set of roquefortine-based secondary metabolites also produced by the wild-type strain. Feeding a number of synthetic HTD analogues to the ΔroqA strain gives rise to the biosynthesis of a number of new roquefortine D derivatives, depending on the nature of the synthetic HTD added. Besides delivering semisynthetic roquefortine analogues, the mutasynthesis studies presented here also shed light on the substrate preferences and molecular mechanisms employed by the roquefortine C/D biosynthesis gene cluster, knowledge that may be tapped for the future development of more complex semisynthetic roquefortine-based secondary metabolites.
authors.affiliation: Leiden Institute of Chemistry, Department of Bio-organic Synthesis, Leiden University, Einsteinweg 55, 2333 CC Leiden (The Netherlands).
authors.forename: Kahina
authors.initials: K
authors.lastname: Ouchaou
authors.forename: Florian
authors.initials: F
authors.lastname: Maire
authors.forename: Oleksandr
authors.initials: O
authors.lastname: Salo
authors.forename: Hazrat
authors.initials: H
authors.lastname: Ali
authors.forename: Thomas
authors.initials: T
authors.lastname: Hankemeier
authors.forename: Gijsbert A
authors.initials: GA
authors.lastname: van der Marel
authors.forename: Dmitri V
authors.initials: DV
authors.lastname: Filippov
authors.forename: Roel A L
authors.initials: RA
authors.lastname: Bovenberg
authors.forename: Rob J
authors.initials: RJ
authors.lastname: Vreeken
authors.forename: Arnold J M
authors.initials: AJ
authors.lastname: Driessen
authors.forename: Herman S
authors.initials: HS
authors.lastname: Overkleeft
mesh_terms: D005656:Fungal Proteins / Q000235:genetics*; D006576:Heterocyclic Compounds, 4 or More Rings / Q000737:chemistry / Q000378:metabolism; D007211:Indoles / Q000737:chemistry* / Q000378:metabolism*; D005810:Multigene Family / Q000235:genetics; D009154:Mutation; D010408:Penicillium chrysogenum / Q000235:genetics* / Q000378:metabolism*; D010879:Piperazines / Q000737:chemistry / Q000378:metabolism
chemical_list: D005656:Fungal Proteins; D006576:Heterocyclic Compounds, 4 or More Rings; D007211:Indoles; D010879:Piperazines; C012536:roquefortine
keywords: Penicillium; alkaloids; antibiotics; diketopiperazines; mutasynthesis; roquefortines