Natural Variation in the ‘Control Loop’ of BVMOAFL210 and Its Influence on Regioselectivity and Sulfoxidation
by
Carmien Tolmie 1
, Rodolpho do Aido-Machado 1, Felix Martin Ferroni 1,2, Martha Sophia Smit 1 and Diederik Johannes Opperman 1,*
Carmien Tolmie 1, Rodolpho do Aido-Machado 1, Felix Martin Ferroni 1,2, Martha Sophia Smit 1 and Diederik Johannes Opperman 1,*
1
University of the Free State, Department of Biotechnology, Bloemfontein 9300, South Africa
2
Universidad Nacional del Litoral/CONICET, Departamento de Física, Santa Fe S3000ZAA, Argentina
*
Author to whom correspondence should be addressed.
Catalysts 2020, 10(3), 339; https://doi.org/10.3390/catal10030339
Received: 21 February 2020 / Revised: 9 March 2020 / Accepted: 9 March 2020 / Published: 19 March 2020
(This article belongs to the Special Issue Flavin Monooxygenases)
Baeyer-Villiger monooxygenases (BVMOs) are flavin-dependent enzymes that primarily convert ketones to esters, but can also catalyze heteroatom oxidation. Several structural studies have highlighted the importance of the ‘control loop’ in BVMOs, which adopts different conformations during catalysis. Central to the ‘control loop’ is a conserved tryptophan that has been implicated in NADP(H) binding. BVMOAFL210 from Aspergillus flavus, however, contains a threonine in the equivalent position. Here, we report the structure of BVMOAFL210 in complex with NADP+ in both the ‘open’ and ‘closed’ conformations. In neither conformation does Thr513 contact the NADP+. Although mutagenesis of Thr513 did not significantly alter the substrate scope, changes in peroxyflavin stability and reaction rates were observed. Mutation of this position also brought about changes in the regio- and enantioselectivity of the enzyme. Moreover, lower rates of overoxidation during sulfoxidation of thioanisole were also observed.
View Full-Text
Keywords:
Baeyer-Villiger monooxygenase; lactone; ester; regioselectivity
▼
Show Figures
Figure 1
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
- Supplementary File 1:
PDF-Document (PDF, 571 KB)
MDPI and ACS Style
Tolmie, C.; do Aido-Machado, R.; Ferroni, F.M.; Smit, M.S.; Opperman, D.J. Natural Variation in the ‘Control Loop’ of BVMOAFL210 and Its Influence on Regioselectivity and Sulfoxidation. Catalysts 2020, 10, 339.
Show more citation formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.
