Download MendeleyDetailed Structure-Function Correlations of Bacillus subtilis Acetolactate Synthase.
Sommer, B., von Moeller, H., Haack, M., Qoura, F., Langner, C., Bourenkov, G., Garbe, D., Loll, B., Bruck, T.(2015) Chembiochem 16: 110-118
- PubMed: 25393087
- DOI: https://doi.org/10.1002/cbic.201402541
- Primary Citation of Related Structures:
4RJI, 4RJJ, 4RJK - PubMed Abstract:
Isobutanol is deemed to be a next-generation biofuel and a renewable platform chemical.1 Non-natural biosynthetic pathways for isobutanol production have been implemented in cell-based and in vitro systems with Bacillus subtilis acetolactate synthase (AlsS) as key biocatalyst.2-6 AlsS catalyzes the condensation of two pyruvate molecules to acetolactate with thiamine diphosphate and Mg(2+) as cofactors. AlsS also catalyzes the conversion of 2-ketoisovalerate into isobutyraldehyde, the immediate precursor of isobutanol. Our phylogenetic analysis suggests that the ALS enzyme family forms a distinct subgroup of ThDP-dependent enzymes. To unravel catalytically relevant structure-function relationships, we solved the AlsS crystal structure at 2.3 Å in the presence of ThDP, Mg(2+) and in a transition state with a 2-lactyl moiety bound to ThDP. We supplemented our structural data by point mutations in the active site to identify catalytically important residues.
Organizational Affiliation:
Fachgebiet Industrielle Biokatalyse, Technische Universität München, Lichtenbergstrasse 4, 85748 Garching (Germany).
