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A Mutasynthesis Approach with a Penicillium chrysogenum Δ roqA Strain Yields New Roquefortine D Analogues
Author(s) -
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.
Publication year - 2015
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201402686
Subject(s) - penicillium chrysogenum , strain (injury) , gene cluster , secondary metabolism , biosynthesis , synthetic biology , chemistry , yield (engineering) , stereochemistry , biology , gene , biochemistry , computational biology , materials science , anatomy , metallurgy
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 Δ roqA 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.