Related Experiment Video
Updated: Jul 5, 2026

Light-driven Enzymatic Decarboxylation
Published on: May 22, 2016
Epothilone C macrolactonization and hydrolysis are catalyzed by the isolated thioesterase domain of epothilone
Christopher N Boddy1, Tanya L Schneider, Kinya Hotta
1Departments of Chemical Engineering, Stanford University, Stanford, California 94305-5025, USA.
Abstract:
Epothilone C is produced by the combined action of one nonribosomal peptide synthetase (NRPS) and nine polyketide synthase (PKS) modules in a multienzyme system. The final step in the biosynthesis is the thioesterase (TE)-catalyzed cyclorelease of epothilone from the EpoF protein. It has been unclear whether isolated PKS TE domains could exhibit macrolactonization activity. Here we demonstrate that the excised epothilone TE domain can catalyze the efficient cyclization of the N-acetylcysteamine thioester of seco-epothilone C to generate epothilone C (kcat/KM = 0.41 +/- 0.03 min-1 mM-1). The TE domain also catalyzes the hydrolysis of both the N-acetylcysteamine thioester of seco-epothilone C (kcat = 0.087 +/- 0.005 min-1, KM = 291 +/- 53 muM) and that of the epothilone C (kcat = 0.67 +/- 0.01 min-1, KM = 117 +/- 5 muM) to form seco-epothilone C.
Related Concept Videos
Catalysis
Acid-Catalyzed Dehydration of Alcohols to Alkenes
Esters to Carboxylic Acids: Acid-Catalyzed Hydrolysis
During hydrolysis, the ester is first activated towards nucleophilic attack through the protonation of the carboxyl oxygen atom by the acid catalyst. The protonation makes the ester carbonyl carbon more electrophilic. In the next step, water acts as a nucleophile and adds to the...
EDTA: Auxiliary Complexing Reagents
Extraction: Advanced Methods
Catalysis

