title: Insights into 6-Methylsalicylic Acid Bio-assembly by Using Chemical Probes.
abstract: Chemical probes capable of reacting with KS (ketosynthase)-bound biosynthetic intermediates were utilized for the investigation of the model type I iterative polyketide synthase 6-methylsalicylic acid synthase (6-MSAS) in vivo and in vitro. From the fermentation of fungal and bacterial 6-MSAS hosts in the presence of chain termination probes, a full range of biosynthetic intermediates was isolated and characterized for the first time. Meanwhile, in vitro studies of recombinant 6-MSA synthases with both nonhydrolyzable and hydrolyzable substrate mimics have provided additional insights into substrate recognition, providing the basis for further exploration of the enzyme catalytic activities.
authors.affiliation: Department of Chemistry University of Warwick Library Road Coventry CV4 7AL UK.
authors.forename: James S
authors.initials: JS
authors.lastname: Parascandolo
authors.affiliation: Department of Chemistry University of Warwick Library Road Coventry CV4 7AL UK.
authors.forename: Judith
authors.initials: J
authors.lastname: Havemann
authors.affiliation: Department of Chemistry University of Cambridge Lensfield Road Cambridge CB2 1EW UK.
authors.forename: Helen K
authors.initials: HK
authors.lastname: Potter
authors.affiliation: Department of Chemistry University of Cambridge Lensfield Road Cambridge CB2 1EW UK; Department of Biochemistry University of Cambridge 80 Tennis Court Road Cambridge CB2 1GA UK.
authors.forename: Fanglu
authors.initials: F
authors.lastname: Huang
authors.affiliation: Department of Chemistry University of Warwick Library Road Coventry CV4 7AL UK.
authors.forename: Elena
authors.initials: E
authors.lastname: Riva
authors.affiliation: Department of Chemistry University of Warwick Library Road Coventry CV4 7AL UK; School of Biosciences The University of Birmingham Birmingham B15 2TT UK.
authors.forename: Jack
authors.initials: J
authors.lastname: Connolly
authors.affiliation: Department of Chemistry University of Warwick Library Road Coventry CV4 7AL UK.
authors.forename: Ina
authors.initials: I
authors.lastname: Wilkening
authors.affiliation: Department of Chemistry University of Warwick Library Road Coventry CV4 7AL UK.
authors.forename: Lijiang
authors.initials: L
authors.lastname: Song
authors.affiliation: Department of Biochemistry University of Cambridge 80 Tennis Court Road Cambridge CB2 1GA UK.
authors.forename: Peter F
authors.initials: PF
authors.lastname: Leadlay
authors.affiliation: Department of Chemistry University of Warwick Library Road Coventry CV4 7AL UK.
authors.forename: Manuela
authors.initials: M
authors.lastname: Tosin
keywords: Chemische Sonden; Dehydratase; Iterative Polyketidkatalyse