English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  Predicted Incorporation of Non-native Substrates by a Polyketide Synthase Yields Bioactive Natural Product Derivatives

Bravo-Rodriguez, K., Ismail-Ali, A. F., Klopries, S., Kushnir, S., Schulz, F., Sanchez-Garcia, E., et al. (2014). Predicted Incorporation of Non-native Substrates by a Polyketide Synthase Yields Bioactive Natural Product Derivatives. ChemBioChem: A European Journal of Chemical Biology, 15(13), 1991-1997. doi:10.1002/cbic.201402206.

Item is

Files

show Files
hide Files
:
cbic_201402206_sm_miscellaneous_information.pdf (Supplementary material), 5MB
Name:
cbic_201402206_sm_miscellaneous_information.pdf
Description:
Supporting information
Visibility:
Public
MIME-Type / Checksum:
application/pdf / [MD5]
Technical Metadata:
Copyright Date:
2014
Copyright Info:
Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim
License:
-

Locators

show

Creators

show
hide
 Creators:
Bravo-Rodriguez, Kenny1, Author              
Ismail-Ali, Ahmed F.2, Author
Klopries, Stephan2, Author
Kushnir, Susanna2, Author
Schulz, Frank2, Author
Sanchez-Garcia, Elsa1, Author              
Ismail, Shehab3, Author
Fansa, Eyad K.3, Author
Wittinghofer, Alfred3, Author
Affiliations:
1Research Group Sánchez-García, Max-Planck-Institut für Kohlenforschung, Max Planck Society, ou_1950289              
2Fakultät für Chemie und Biochemie, Ruhr-Universität Bochum, Universitätsstrasse 150, 44780 Bochum (Germany), ou_persistent22              
3Sonstige Wissenschaftliche Organisationseinheit, ou_persistent22              

Content

show
hide
Free keywords: computational chemistry; free energy calculations; molecular dynamics; monensin; polyketide biosynthesis; QM/MM
 Abstract: The polyether ionophore monensin is biosynthesized by a polyketide synthase that delivers a mixture of monensins A and B by the incorporation of ethyl- or methyl-malonyl-CoA at its fifth module. Here we present the first computational model of the fifth acyltransferase domain (AT5mon) of this polyketide synthase, thus affording an investigation of the basis of the relaxed specificity in AT5mon, insights into the activation for the nucleophilic attack on the substrate, and prediction of the incorporation of synthetic malonic acid building blocks by this enzyme. Our predictions are supported by experimental studies, including the isolation of a predicted derivative of the monensin precursor premonensin. The incorporation of non-native building blocks was found to alter the ratio of premonensins A and B. The bioactivity of the natural product derivatives was investigated and revealed binding to prenyl-binding protein. We thus show the potential of engineered biosynthetic polyketides as a source of ligands for biological macromolecules.

Details

show
hide
Language(s): eng - English
 Dates: 2014-04-302014-07-152014-09-05
 Publication Status: Published in print
 Pages: 7
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1002/cbic.201402206
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: ChemBioChem : A European Journal of Chemical Biology
  Other : ChemBioChem
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: Weinheim, Germany : Wiley-VCH
Pages: 7 Volume / Issue: 15 (13) Sequence Number: - Start / End Page: 1991 - 1997 Identifier: ISSN: 1439-4227
CoNE: https://pure.mpg.de/cone/journals/resource/110978984568897_1