PMID- 26833898 OWN - NLM STAT- MEDLINE DCOM- 20161213 LR - 20240325 IS - 1521-3773 (Electronic) IS - 1433-7851 (Print) IS - 1433-7851 (Linking) VI - 55 IP - 10 DP - 2016 Mar 1 TI - Insights into 6-Methylsalicylic Acid Bio-assembly by Using Chemical Probes. PG - 3463-7 LID - 10.1002/anie.201509038 [doi] AB - 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. CI - (c) 2015 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. FAU - Parascandolo, James S AU - Parascandolo JS AD - Department of Chemistry, University of Warwick, Library Road, Coventry, CV4 7AL, UK. FAU - Havemann, Judith AU - Havemann J AD - Department of Chemistry, University of Warwick, Library Road, Coventry, CV4 7AL, UK. FAU - Potter, Helen K AU - Potter HK AD - Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK. FAU - Huang, Fanglu AU - Huang F AD - Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK. AD - Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge, CB2 1GA, UK. FAU - Riva, Elena AU - Riva E AD - Department of Chemistry, University of Warwick, Library Road, Coventry, CV4 7AL, UK. FAU - Connolly, Jack AU - Connolly J AD - Department of Chemistry, University of Warwick, Library Road, Coventry, CV4 7AL, UK. AD - School of Biosciences, The University of Birmingham, Birmingham, B15 2TT, UK. FAU - Wilkening, Ina AU - Wilkening I AD - Department of Chemistry, University of Warwick, Library Road, Coventry, CV4 7AL, UK. FAU - Song, Lijiang AU - Song L AD - Department of Chemistry, University of Warwick, Library Road, Coventry, CV4 7AL, UK. FAU - Leadlay, Peter F AU - Leadlay PF AD - Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge, CB2 1GA, UK. FAU - Tosin, Manuela AU - Tosin M AD - Department of Chemistry, University of Warwick, Library Road, Coventry, CV4 7AL, UK. m.tosin@warwick.ac.uk. LA - eng GR - BB/J007250/1/Biotechnology and Biological Sciences Research Council/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160202 PL - Germany TA - Angew Chem Int Ed Engl JT - Angewandte Chemie (International ed. in English) JID - 0370543 RN - 0 (Molecular Probes) RN - 0 (Salicylates) RN - L5352FE23Y (6-methylsalicylic acid) SB - IM MH - Chromatography, High Pressure Liquid MH - *Molecular Probes MH - Salicylates/*metabolism PMC - PMC4797705 OTO - NOTNLM OT - chemical probes OT - dehydratase OT - iterative polyketide catalysis EDAT- 2016/02/03 06:00 MHDA- 2016/12/15 06:00 PMCR- 2016/03/18 CRDT- 2016/02/03 06:00 PHST- 2015/09/26 00:00 [received] PHST- 2015/11/19 00:00 [revised] PHST- 2016/02/03 06:00 [entrez] PHST- 2016/02/03 06:00 [pubmed] PHST- 2016/12/15 06:00 [medline] PHST- 2016/03/18 00:00 [pmc-release] AID - ANIE201509038 [pii] AID - 10.1002/anie.201509038 [doi] PST - ppublish SO - Angew Chem Int Ed Engl. 2016 Mar 1;55(10):3463-7. doi: 10.1002/anie.201509038. Epub 2016 Feb 2.