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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.

SUBMITTER: Parascandolo JS 

PROVIDER: S-EPMC4950124 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Insights into 6-Methylsalicylic Acid Bio-assembly by Using Chemical Probes.

Parascandolo James S JS   Havemann Judith J   Potter Helen K HK   Huang Fanglu F   Riva Elena E   Connolly Jack J   Wilkening Ina I   Song Lijiang L   Leadlay Peter F PF   Tosin Manuela M  

Angewandte Chemie (Weinheim an der Bergstrasse, Germany) 20160202 10


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 wi  ...[more]

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