Purification and Kinetic Characterization of the Essential Condensation Enzymes Involved in Prodiginine and Tambjamine Biosynthesis
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Authors
Picott, Katherine Joy
Deichert, Julie Amanda
deKemp, Ella Marie
Snieckus, Victor
Ross, Avena C.
Date
2019
Type
preprint
Language
en
Keyword
Natural Products , Prodiginines , Condensation Enzymes , Biosynthesis
Alternative Title
Abstract
Prodiginines and tambjamines are related families of bioactive alkaloid natural products with pharmaceutical potential. Both compound families result from a convergent biosynthetic pathway ending in the condensation of a conserved bipyrrole core with a variable partner. This reaction is performed by unique condensation enzymes, and has the potential to be manipulated to produce new pyrrolic compounds. We have purified and reconstituted the in vitro activity of the condensation enzymes‐ PigC and TamQ, from Pseudoalteromonas sp., involved respectively in prodiginine and tambjamine biosynthetic pathways. Kinetic analysis confirmed a Uni Uni Bi Uni ping‐pong reaction sequence with competitive and uncompetitive substrate inhibition for PigC and TamQ respectively. The kinetic parameters of each enzyme provide insight into their differing substrate scope, and suggest that TamQ may have evolved a wide substrate tolerance that can be utilized for the production of novel prodiginines and tambjamine.
Description
Citation
Publisher
Wiley
License
This is the peer reviewed version of the following article: ChemBioChem 10.1002/cbic.201900503, which has been published in final form at https://doi.org/10.1002/cbic.201900503. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.