2.2.1.6 evolution acetolactate synthase and pyruvate decarboxylase are both thiamine diphosphate-dependent enzymes that use pyruvate as a substrate, but they produce different products.Whereas pyruvate decarboxylase catalyzes the non-oxidative decarboxylation of pyruvate to acetaldehyde, acetolactate synthase, which is involved in the biosynthesis of branched amino acids (Val, Leu, Ile), catalyzes the carboligation between two pyruvate molecules to form an acetolactate molecule and carbon dioxide, structural and functional similarities of the enzymes, overview -, 735039 2.2.1.6 evolution the enzyme belongs to the ALS enzyme family that forms a distinct subgroup of ThDP-dependent enzymes. The ALS subfamily differs significantly in structure and possibly in catalytic mechanism, phylogenetic analysis. The ThDP-dependent enzymes cluster into three distinct sequence groups: acetolactate synthases, acetohydroxyacid synthases, and carboxylases. Eventhough ALS and AHAS catalyze the same reaction, they show different cofactors and domain structure: AHAS family enzymes have both catalytic and regulatory subunits, structure comparisons, overview -, 733658 2.2.1.6 evolution three types of isozymes, AHAS I, II, III, are found in Enterobacteria encoded by ilvBN, ilvGMEDA, ilvIH operons, respectively. Bacterial AHAS consists of a regulatory and a catalytic subunit -, 733685 2.2.1.6 evolution two types of ALSs, anabolic acetohydroxyacid synthase (AHAS) and catabolic ALSs (cALS). The anabolic AHAS is primarily found in plants, fungi, and bacteria, is involved in the biosynthesis of branched-chain amino acids, and contains FAD, whereas the cALS is found only in some bacteria and is involved in the butanediol fermentation pathway. Both of the enzymes are thiamine diphosphate-dependent and require a divalent metal ion for catalytic activity. The catabolic ALS can be distinguished from anabolic AHAS by a low optimal pH of about pH 6.0, FAD-independent functionality, a genetic location within the butanediol operon, and lack of a regulatory subunit. In all of the crystal structures of ThDP-dependent enzymes determined to date, with the exception of glyoxylate carbo-ligase (GCL), a highly conerved glutamate residue is found at hydrogen-bonding distance from the N1' atom of the aminopyrimidine ring of the boundThDP and plays a key role in catalysis. In Enterococcus faecalis it is Glu49 733597 2.2.1.6 malfunction deletion of the als gene abolishes acetoin production. Deletion of gene als in an engineered strain of Pyrococcus furiosus containing an additional pathway for ethanol production significantly improves the yield of ethanol 734625 2.2.1.6 malfunction deletion of the enzyme gene abolishes acetoin production 734625 2.2.1.6 malfunction enzyme inhibition abolishes biosynthesis of brachend chain amino acids and leads to bacteriostasis -, 733685 2.2.1.6 malfunction the A205F substitution in acetolactate synthase, confirmed in a population of allotetraploid annual bluegrass, confers resistance to imidazolinone, sulfonylurea, triazolopyrimidines, sulfonylaminocarbonyl triazolinones, and pyrimidinyl(thio)benzoate herbicides 734994 2.2.1.6 malfunction the als defective strain, which is incapable of producing C4 compounds, appears sensitive to pyruvate under acidic conditions rendering it unable to grow. Accordingly, the als-mutant strain shows a simultaneous inability to alkalinize internal and external media -, 733995 2.2.1.6 malfunction the conserved His84 and Gln86 residues lie in the catalytic dimer interface of the enzyme. Mutational analyses of these invariants lead to significant reduction in their activity with reduced affinity toward the substrate -, 733747 2.2.1.6 malfunction the deletion mutants DELTAMoilv2 and DELTAMoilv6 are both auxotrophic for leucine, isoleucine and valine, and are defective in conidial morphogenesis, appressorial penetration and pathogenicity, phenotypes, overview -, 734734 2.2.1.6 malfunction the enzyme-deficient strain cannot produce acetoin, 2,3-butanediol, and L-valine -, 756209 2.2.1.6 malfunction the sulfonylurea-resistant plants, found in a population from paddy fields in Japan, harbor amino acid substitutions at Pro197 or Trp574 in either ALS1 or ALS2 (the amino acid number is standardized to the Arabidopsis thaliana sequence) 735336 2.2.1.6 metabolism acetohydroxyacid synthase is the key enzyme in branched chain amino acid biosynthesis pathway, overview 733241 2.2.1.6 metabolism acetohydroxyacid synthase or asacetolactate synthase catalyzes the first step in the biosynthe-sis of branched-chain amino acids such as isoleucine, leucine, and valine. This reaction involves synthesizing either (2S)-acetolactate from two molecules of pyruvate or (2S)-2-aceto-2-hydroxybutyrate from pyruvate and 2-oxobutyrate -, 733747 2.2.1.6 metabolism acetolactate synthase catalyses the first common step in leucine, isoleucine and valine biosynthesis -, 734734 2.2.1.6 metabolism acetolactate synthase is a thiamine diphosphate-dependent enzyme that is involved in the biosynthesis of branched amino acids (Val, Leu, Ile), catalyzing the carboligation between two pyruvate molecules to form an acetolactate molecule and carbon dioxide -, 735039 2.2.1.6 metabolism enzyme AHAS catalyses the condensation of either two molecules of pyruvate to form acetolactate in the leucine and valine pathway, or of one molecule of pyruvate with one molecule of 2-oxobutyrate toform 2-aceto-2-hydroxybutyrate as the first step in the isoleucine biosynthesis -, 734978 2.2.1.6 metabolism enzyme overexpression can effectively improve acetoin/2,3-butanediol and L-valine production in Bacillus licheniformis -, 756209 2.2.1.6 metabolism fermentation pathways in Klebsiella pneumoniae, overview. The biosynthesis route of 2,3-BD in Klebsiella pneumoniae proceeds via pyruvate, acetolactate, and acetoin to 2,3-BD. 2,3-BD production from pyruvate involves three enzymes, namely, 2-acetolactate synthase (ALS), 2-acetolactate decarboxylase (ALDC), and acetoin reductase (AR). These enzymes catalyze the production of acetolactate from pyruvate, acetoin from acetolactate, and 2,3-BD from acetoin -, 733547 2.2.1.6 metabolism isoform Ilv2 plays a crucial role in isoleucine and valine biosynthesis, isoform Ilv6 contributes to isoleucine and leucine biosynthesis -, 734734 2.2.1.6 metabolism key enzyme for the biosynthesis of branched-chain amino acids (valine, leucine and isoleucine) that are required for plant growth 734841 2.2.1.6 metabolism strain IL1403 is able to cometabolize pyruvate and glucose at low pH, producing lactate, acetate as well as diacetyl/acetoin compounds. The enzyme is involved in the pyruvate metabolism in Lactococcus lactis, overview -, 733995 2.2.1.6 metabolism the bacterial anabolic enzyme form catalyzes the first step in biosynthesis of branched amino acids isoleucine, leucine and valine. It catalyzes the first and the most crucial step which is either the self condensation of pyruvate to form 2-acetolactate or the condensation between lactate and 2-ketobutyrate to form 2-aceto-2-hydroxybutyrate. 2-acetolactate and 2-aceto-2-hydroxybutyrate serve as the precursors for the synthesis of leucine and valine while latter serves as the precursor for the synthesis of isoleucine. In some bacteria, the enzyme is responsible for the formation of butanediol and other products of fermentation -, 733685 2.2.1.6 metabolism the bacterial anabolic enzyme form catalyzes the first step in biosynthesis of branched amino acids isoleucine, leucine and valine. It catalyzes the first and the most crucial step which is either the self condensation of pyruvate to form 2-acetolactate or the condensation between lactate and 2-oxobutyrate to form 2-aceto-2-hydroxybutyrate. 2-acetolactate and 2-aceto-2-hydroxybutyrate serve as the precursors for the synthesis of leucine and valine while latter serves as the precursor for the synthesis of isoleucine. In some bacteria, the enzyme is responsible for the formation of butanediol and other products of fermentation 733685 2.2.1.6 metabolism the enzyme catalyzes the first step in biosynthesis of branched amino acids isoleucine, leucine and valine 733685 2.2.1.6 metabolism the enzyme is involved in the branched chain amino acid biosynthesis -, 733745 2.2.1.6 metabolism the first enzyme of the biosynthetic pathway that produces the branched-chain of the essential amino acids L-valine, L-leucine, and L-isoleucine 756568 2.2.1.6 metabolism there are two enzymes in nature that are known to produce 2-acetolactate from pyruvate, a catabolic ALS encoded by the alsSD operon, which is involved in the production of acetoin and butanediol, and ananabolic 2-acetohydroxyacid synthase (AHAS) that participates in biosynthesis of the branched chain amino acids isoleucine, leucine and valine. The flux of 2-acetolactate toward amino acid biosynthesis is regulated via allosteric activation of 2-acetolactate decarboxylase, ALDC, by either valine or leucine 734625 2.2.1.6 additional information active site structure, catalytically relevant structure-function relationships, overview -, 733658 2.2.1.6 additional information homology modeling of Mycobacterium tuberculosis enzyme is performed by using crystal structures, PDB IDs 1N0H and 1JSC, from the Saccharomyces cerevisiae enzyme as template, molcular dynamics simulation -, 733747 2.2.1.6 additional information molecular dynamics simulation studies suggest that the conserved His84 and Gln86 residues residues are likely to play a key role in maintaining the Glu85 side chain in the required geometry with N1'atom of thiamine diphosphate during catalysis -, 733747 2.2.1.6 additional information structure homology modeling -, 733745 2.2.1.6 additional information structure homology modeling of wild-type enzyme and H474R enzyme mutant, structure comparisons, overview -, 735039 2.2.1.6 additional information the catabolic enzyme form lacks a regulatory subunit. Residue His 111, which is widely present as phenylalanine in many other ThDP-dependent enzymes, plays a crucial role in substrate binding, importance of residues H111, Q112, and Q411 residues for catalysis, Q112 and Q411 might be involved in thiamine diphosphate binding, enzyme structure homology modeling, overview 733987 2.2.1.6 additional information the domains are crucial to the function of MoIlv2 and MoIlv6 during pathogenicity on rice and barley leaves, functional analysis of enzyme domains, overview -, 734734 2.2.1.6 additional information there exist two types of the enzyme, catabolic and anabolic AHAS. The anabolic form of the enzyme consists of two subunits out of which one is catalytic while the other is regulatory in nature. The regulatory subunit acts via feedback inhibition -, 733685 2.2.1.6 additional information wild-type and mutant H28A/N484A active site structure analysis, PDB IDs 2PGN and 4D5G -, 733089 2.2.1.6 physiological function catabolic acetolactate synthase from Enterococcus faecalis is a FAD-independent enzyme, which catalyzes the condensation of two molecules of pyruvate to produce acetolactate 733987 2.2.1.6 physiological function complete inactivation of the acetolactate synthase in Corynebacterium glutamicum DM1729 and DM1933 by deletion of the ilvB gene, encoding the catalytic subunit, leads to L-valine, L-isoleucine, and L-leucine auxotrophy and to improved L-lysine production 695780 2.2.1.6 physiological function deletion of gene ilv2 encoding acetolactate synthase results in loss of viability during isoleucine and valine starvation due to 2-oxobutanoate accumulation. Rapamycin further decreases vialbility of the mutant. Recovery from starvation is influenced by the carbon source present during recovery 700065 2.2.1.6 physiological function deletion of gene ilv2 encoding acetolactate synthase results in significant attenuation of virulence and a grater than 100fold reduction in viability after only four hours of isoleucine and valine starvation due to 2-oxobutanoate accumulation. Rapamycin increases vialbility of both ilv1 and ilv2 mutants. Recovery from starvation is influenced by the carbon source present during starvation 700065 2.2.1.6 physiological function MoIlv2 plays a crucial role in isoleucine and valine biosynthesis, whereas MoIlv6 contributes to isoleucine and leucine biosynthesis, both genes are required for fungal pathogenicity. MoIlv2 and MoIlv6 play a critical role in maintaining the balance of intracellular amino acid levels. And MoIlv2 and MoIlv6 are involved in aerial hyphal growth, pigmentation, conidial morphogenesis and pathogenicity on rice and barley -, 734734 2.2.1.6 physiological function Pyrococcus furiosus produces acetoin as amajor end product at growth temperatures below 85°C in a temperature-dependent manner via a acetolactate synthase whose gene expression and biochemical function are temperature-dependent 734625 2.2.1.6 physiological function the enzyme contributes to pH homeostasis in acid stress conditions -, 733995 2.2.1.6 physiological function the enzyme is involved in the production of acetoin (3-hydroxybutanone) as a major product at growth temperatures below 80°C. Acetoin is produced by wild-type Pyrococcus furiosus during growth at sub-optimal temperatures below 80°C 734625 2.2.1.6 physiological function the enzyme plays a critical role in maintaining the balance of intracellular amino acid level, is involved in aerial hyphal growth, pigmentation, conidial morphogenesis, and is required for fungal pathogenicity -, 734734 2.2.1.6 physiological function transformation of a H+-ATPase defective strain with a C-terminal truncation of acetohydroxyacid synthase gene ilvBN results in increased valine production from 21.7 mM for wild-type to 46.7 mM and increase in the valine intermediate acetoin. Inserting acetohydroxyacid isomeroreductase gene into the ilvBN plasmid further increases valine producion 696827