title: Rational domain swaps decipher programming in fungal highly reducing polyketide synthases and resurrect an extinct metabolite.
abstract: The mechanism of programming of iterative highly reducing polyketide synthases remains one of the key unsolved problems of secondary metabolism. We conducted rational domain swaps between the polyketide synthases encoding the biosynthesis of the closely related compounds tenellin and desmethylbassianin. Expression of the hybrid synthetases in Aspergillus oryzae led to the production of reprogrammed compounds in which the changes to the methylation pattern and chain length could be mapped to the domain swaps. These experiments reveal for the first time the origin of programming in these systems. Domain swaps combined with coexpression of two cytochrome P450 encoding genes from the tenellin biosynthetic gene cluster led to the resurrection of the extinct metabolite bassianin.
authors: School of Chemistry, University of Bristol, Cantock's Close, Bristol BS8 1TS, UK.
authors: Katja M
authors: KM
authors: Fisch
authors: Walid
authors: W
authors: Bakeer
authors: Ahmed A
authors: AA
authors: Yakasai
authors: Zhongshu
authors: Z
authors: Song
authors: Jennifer
authors: J
authors: Pedrick
authors: Zahida
authors: Z
authors: Wasil
authors: Andrew M
authors: AM
authors: Bailey
authors: Colin M
authors: CM
authors: Lazarus
authors: Thomas J
authors: TJ
authors: Simpson
authors: Russell J
authors: RJ
authors: Cox
mesh_terms: D001236:Aspergillus oryzae / Q000201:enzymology*; D008958:Models, Molecular; D010084:Oxidation-Reduction; D048630:Polyketide Synthases / Q000737:chemistry / Q000378:metabolism*; D011728:Pyridones / Q000737:chemistry / Q000378:metabolism
chemical_list: D011728:Pyridones; C108585:bassianin; C015528:tenellin; D048630:Polyketide Synthases