A Mutasynthesis Approach with a Penicillium chrysogenum ΔroqA Strain Yields New Roquefortine D Analogues. Issue 6 (12th March 2015)

• Record Type: Journal Article
• Authors: Ouchaou, Kahina; Maire, Florian; Salo, Oleksandr; Ali, Hazrat; Hankemeier, Thomas; van der Marel, Gijsbert A.; Filippov, Dmitri V.; Bovenberg, Roel A. L.; Vreeken, Rob J.; Driessen, Arnold J. M.; Overkleeft, Herman S.
• Is Part Of: Chembiochem. Volume 16:Issue 6(2015)
• Page Start: 915
• Page End: 923
• Publication Date: 2015-03-12
• Subjects: Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1002/cbic.201402686
• Languages: English
• ISSNs: 1439-4227

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p> <italic>Penicillium chrysogenum</italic>, which lacks the <italic>roqA</italic> 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 Δ<italic>roqA</italic> 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.</p> </abstract>