Detailed structure-function correlations of Bacillus subtilis acetolactate synthase.

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Sommer B, von Moeller H, Haack M, Qoura F, Langner C, Bourenkov G, Garbe D, Loll B, Bruck T

Detailed structure-function correlations of Bacillus subtilis acetolactate synthase.

Chembiochem. 2015 Jan 2;16(1):110-8. doi: 10.1002/cbic.201402541. Epub 2014 Nov 13.

PubMed ID

25393087 [ View in PubMed

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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 A 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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Cocarboxylase	Acetolactate synthase, catabolic	Protein	Klebsiella pneumoniae	Unknown	Cofactor Product of	Details