Details
| Original language | English |
|---|---|
| Pages (from-to) | 18469-18476 |
| Number of pages | 8 |
| Journal | RSC Advances |
| Volume | 10 |
| Issue number | 31 |
| Publication status | Published - 15 May 2020 |
Abstract
A structural model of the enoyl reductase (ER) catalytic domain of the fungal highly-reducing polyketide synthase squalestatin tetraketide synthase (SQTKS) was developed. Simulated docking of substrates and inhibitors allowed the definition of active site residues involved in catalysis and substrate selectivity. These were investigatedin silicowith the aim of extending the substrate scope. Residues were identified which limit the substrate selectivity of the SQTKS ER, and these were mutated and the engineered ER domain assayedin vitro. Significant changes to the programming of the mutant SQTKS ER domains were observed allowing the processing of longer and more methylated substrates.
ASJC Scopus subject areas
- Chemistry(all)
- General Chemistry
- Chemical Engineering(all)
- General Chemical Engineering
Cite this
- Standard
- Harvard
- Apa
- Vancouver
- BibTeX
- RIS
In: RSC Advances, Vol. 10, No. 31, 15.05.2020, p. 18469-18476.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - Reengineering the programming of a functional domain of an iterative highly reducing polyketide synthase
AU - Piech, Oliver
AU - Cox, Russell John
N1 - Funding Information: DFG is thanked for the provision of preparative LCMS and NMR instrumentation (INST 187/621-1, INST 187/686-1). The Leibniz University of Hannover is thanked for the provision of a studentship position (OP). The publication of this article was funded by the Open Access Fund of the Leibniz Universität Hannover.
PY - 2020/5/15
Y1 - 2020/5/15
N2 - A structural model of the enoyl reductase (ER) catalytic domain of the fungal highly-reducing polyketide synthase squalestatin tetraketide synthase (SQTKS) was developed. Simulated docking of substrates and inhibitors allowed the definition of active site residues involved in catalysis and substrate selectivity. These were investigatedin silicowith the aim of extending the substrate scope. Residues were identified which limit the substrate selectivity of the SQTKS ER, and these were mutated and the engineered ER domain assayedin vitro. Significant changes to the programming of the mutant SQTKS ER domains were observed allowing the processing of longer and more methylated substrates.
AB - A structural model of the enoyl reductase (ER) catalytic domain of the fungal highly-reducing polyketide synthase squalestatin tetraketide synthase (SQTKS) was developed. Simulated docking of substrates and inhibitors allowed the definition of active site residues involved in catalysis and substrate selectivity. These were investigatedin silicowith the aim of extending the substrate scope. Residues were identified which limit the substrate selectivity of the SQTKS ER, and these were mutated and the engineered ER domain assayedin vitro. Significant changes to the programming of the mutant SQTKS ER domains were observed allowing the processing of longer and more methylated substrates.
UR - http://www.scopus.com/inward/record.url?scp=85085734500&partnerID=8YFLogxK
U2 - 10.1039/d0ra04026f
DO - 10.1039/d0ra04026f
M3 - Article
AN - SCOPUS:85085734500
VL - 10
SP - 18469
EP - 18476
JO - RSC Advances
JF - RSC Advances
SN - 2046-2069
IS - 31
ER -