Acetohydroxy acid synthase AHAS

Inhibition of acetolactate synthase (ALS) [Acetohydroxy acid synthase (AHAS)] Sulfonylureas Imidazolinones T riazolopyrimidines Pyrimidinylthiobenzoates 2... 

Valine overproduction inf. coli K-12 using random mutant strains is unknown. However, systems metaboUc engineering approaches allowed titers of 7.3 g 1 by several methods [27]. Acetohydroxy acid synthase (AHAS), encoded by ilvl, was mutated to remove feedback inhibition. Competing pathways toward leucine. 

Acetolactate synthase, ALS, also referred to as acetohydroxy acid synthase, AHAS, is the first common enzyme in the biosynthetic pathway to the branched-chain amino acids valine, leucine and isoleucine (Fig. 1). 

Compounds 296-299 inhibit acetohydroxy acid synthase (AHAS), formerly known as acetolactate synthase. Its activity is not present in animals, but it has been found in all plants where measurements have been attempted. Acetohydroxy acid synthase catalyses the first step in production of branched amino acids (leucine, valine and isoleucine) (Scheme 73), which are obviously needed for the protein synthesis and cell growth. The compounds 296-299 seem to bind within the substrate-access channel of the enzyme, thus blocking a-ketocarboxylate access to the active site. While these herbicides are undoubtedly highly successful, resistance developed due to mutations within AHAS is becoming a serious problem [274, 275]. 

Figure 15.4 Isobutanol and 2-methyl butanol (2MB) production via keto acid pathway in cyanobacteria. Gene/protein symbols are dmA, citramalate synthase leuCD, isopropylmalate isomerase leuB, 3-isopropylmalate dehydrogenase AHAS, acetohydroxyacid synthase ilvC, acetohydroxy acid isomeroreductase ilvD, dihydroxy acid dehydratase kivd, ketoisovalerate decarboxylase yqhD, alcohol dehydrogenase.

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