Recent Advances in Understanding the Mechanism and Inhibition of Acetolactate Synthase

  • John V. Schloss
Part of the Chemistry of Plant Protection book series (PLANT PROTECTIO, volume 10)


A review of our current understanding of the structure of acetolactate synthase, the molecular mechanism of its inhibition by herbicides, and how this inhibition is translated into phytotoxicity in vivo, is presented.


Singlet Oxygen Flavin Adenine Dinucleotide Pyruvate Decarboxylase Oxygenase Activity Thiamine Pyrophosphate 
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  1. 1.
    Crout DHG (1990) The chemistry of branched chain amino acids biosynthesis: stereochemical and mechanistic aspects, In: Barak Z, Chipman DM, Schloss JV (eds) Biosynthesis of Branched Chain Amino Acids. VCH, Weinheim, pp 199–242Google Scholar
  2. 2.
    Crout DHG, Lee ER, Rathbone DL (1990) Absolute configuration of the product of the acetolactate synthase reaction by a novel method of analysis using acetolactate decarboxylase, J Chem Soc, Perkin Trans 1, 1367–1369CrossRefGoogle Scholar
  3. 3.
    Schloss JV (1992) Acetolactate synthase, In: Müller F (ed) Chemistry and Biochemistry of Flavoenzymes, Vol. III, pp 531–542Google Scholar
  4. 4.
    Grimminger H, Umbarger HE (1979) Acetohydroxy acid synthase I of Escherichia coli, purification and properties, J Bacteriol 137, 846–853PubMedGoogle Scholar
  5. 5.
    Durner J, Böger P (1990) Oligomeric forms of plant acetolactate synthase depend on flavin adenine dinucleotide, Plant Physiol 93, 1027–1031PubMedCrossRefGoogle Scholar
  6. 6.
    Singh BK, Newhouse KE, Stidham MA, Shaner DL (1990) Imidazolinones and acetohydroxyacid synthase from plants. In: Barak Z, Chipman DM, Schloss JV (eds) Biosynthesis of Branched Chain Amino Acids, pp 357–371Google Scholar
  7. 7.
    Koland JG, Miller MJ, Gennis RB (1984) Reconstitution of the membrane bound ubiquinone dependent pyruvate oxidase respiratory chain of Escherichia coli with cytochrome D terminal oxidase, Biochemistry 23, 445–453PubMedCrossRefGoogle Scholar
  8. 8.
    Muller YA, Schulz GE (1993) Structure of the thiamine- and flavin-dependent enzyme pyruvate oxidase, Science 259, 965–967PubMedCrossRefGoogle Scholar
  9. 9.
    Green JBA (1989) Pyruvate decarboxylase is like acetolactate synthase (ILV2) and not like pyruvate dehydrogenase E1 subunit, FEBS Lett 246, 1–5PubMedCrossRefGoogle Scholar
  10. 10.
    Dyda F, Furey W, Swaminathan S, Sax M, Farrenkopf B, Jordan F (1993) Catalytic centers in the thiamine diphosphate dependent enzyme pyruvate decarboxylase at 2.4 Å resolution, Biochemistry 32, 6165–6170PubMedCrossRefGoogle Scholar
  11. 11.
    Lindqvist Y, Schneider G, Ermler U, Sundstroem M (1992) Three-dimensional structure of transketolase, a thiamine diphosphate dependent enzyme, at 2.5 Å resolution, EMBO J 11, 2373–2379PubMedGoogle Scholar
  12. 12.
    Kluger R (1987) Thiamine diphosphate: a mechanistic update on enzymic and nonenzymic catalysis of decarboxylation, Chem Rev 87, 863–876CrossRefGoogle Scholar
  13. 13.
    Suchy J, Mieyal J J, Bantle G, Sable HZ (1972) Coenzyme interactions. VI Properties of the pyrimidine moiety of thiamine, J Biol Chem 247, 5905–5912PubMedGoogle Scholar
  14. 14.
    Schloss JV, Aulabaugh A (1990) Acetolactate synthase and ketol-acid reductoisomerase: a search for reason and a reason for search. In: Barak Z, Chipman DM, Schloss JV (eds) Biosynthesis of Branched Chain Amino Acids. VCH, Weinheim, pp 329–356Google Scholar
  15. 15.
    Schloss JV, Ciskanik LM, Van Dyk DE (1988) Origin of the herbicide binding site of acetolactate synthase, Nature (London) 331, 360–362CrossRefGoogle Scholar
  16. 16.
    Sathasivan K, Haughn GW, Murai N (1991) Molecular basis of imidazolinone herbicide resistance in Arabidopsis thaliana var Columbia, Plant Physiol 97, 1044–1050PubMedCrossRefGoogle Scholar
  17. 17.
    Saxena PK, King J (1990) Lack of cross-resistance of imidazolinone-resistant cell lines of Datura innoxia P Mill. to chlorsulfuron, Plant Physiol 94, 1111–1115PubMedCrossRefGoogle Scholar
  18. 18.
    Wittenbach VA, Rayner DR, Schloss JV (1992) Pressure points in the biosynthetic pathway for branched-chain amino acids. In: Singh BK, Flores HE, Shannon JC (eds) Biosynthesis and Molecular Regulation of Amino Acids in Plants. American Society of Plant Physiologists, Rockville, pp 69–88Google Scholar
  19. 19.
    Butler J, Siehl D (1992) The inhibitor binding pocket of acetolactate synthase from Kochia scoparia. In: Singh BK, Flores HE, Shannon JC (eds) Biosynthesis and Molecular Regulation of Amino Acids in Plants. American Society of Plant Physiologists, Rockville, p 361Google Scholar
  20. 20.
    Subramanian MV, Gallant V, Dias JM, Mireles JC (1991) Acetolactate synthase inhibitors bind to the regulatory site, Plant Physiol 96, 310–313PubMedCrossRefGoogle Scholar
  21. 21.
    Hawkes TR, Howard JL, Pontin SE (1989) Herbicides that inhibit the biosynthesis of branched chain amino acids. In: Dodge A (ed) Herbicides and Plant Metabolism, Seminar Series 38. Cambridge University Press, Cambridge, pp 113–136Google Scholar
  22. 22.
    Hawkes TR (1989) Studies of herbicides which inhibit branched chain amino acid biosynthesis. In: Copping LG, Dalziel J, Dodge AD (eds) Prospects for Amino Acid Biosynthesis Inhibitors in Crop Protection and Pharmaceutical Chemistry. The Lavenham Press Limited, Lavenham, pp 131–138Google Scholar
  23. 23.
    Muhitch MJ, Shaner DL, Stidham MA (1987) Imidazolinones and acetohydroxyacid synthase from plants. Properties of the enzyme from maize suspension culture cells and evidence for the binding of imazapyr to acetohydroxyacid synthase in vivo, Plant Physiol 83, 451–456PubMedCrossRefGoogle Scholar
  24. 24.
    Shaner DL, Singh BK, Stidham MA (1990) Interaction of imidazolinones with plant acetohydroxyacid synthase: evidence for in vivo binding and competition with sulfometuron methyl, J Agric Food Chem 38, 1279–1282CrossRefGoogle Scholar
  25. 25.
    Shaner DL, Singh BK (1991) Imidazolinone-induced loss of acetohydroxyacid synthase activity in maize is not due to the enzyme degradation, Plant Physiol 97, 1339–1341PubMedCrossRefGoogle Scholar
  26. 26.
    Durner J, Gailus V, Böger P (1991) New aspects on inhibition of plant acetolactate synthase by chlorsulfuron and imazaquin, Plant Physiol 95, 1144–1149PubMedCrossRefGoogle Scholar
  27. 27.
    Abell LM, Schloss JV (1991) Oxygenase side reactions of acetolactate synthase and other carbanion-forming enzymes, Biochemistry 30: 7883–7887PubMedCrossRefGoogle Scholar
  28. 28.
    Bertagnolli BL, Hager LP (1993) Role of flavin in acetoin production by two bacterial pyruvate oxidases, Arch Biochem Biophys 300: 364–371PubMedCrossRefGoogle Scholar
  29. 29.
    Tse JM-T, Schloss JV (1993) The oxygenase reaction of acetolactate synthase, Biochemistry, 32: 10398–10403PubMedCrossRefGoogle Scholar
  30. 30.
    Abell LM, Schloss JV (1993) Use of the oxygenase activity of acetolactate synthase for herbicide detection. US Patent 5,206,135, 28 December 1990Google Scholar
  31. 31.
    Schloss JV, Van Dyk DE, Vasta JF, Kutny RM (1985) Purification and properties of Salmonella typhimurium acetolactate synthase isozyme II from Escherichia coli HB101/pDU9, Biochemistry 24, 4952–4959PubMedCrossRefGoogle Scholar
  32. 32.
    Hartman FC, Harpel MR (1993) Chemical and genetic probes of the active site of D-ribulose 1,5-bisphosphate carboxylase/oxygenase: a retrospective based on the three dimensional structure, Advances Enzymol 67, 1–76Google Scholar
  33. 33.
    Lorimer GH, Andrews TJ, Tolbert NE (1973) Ribulose diphosphate oxygenase. II. Further proof of reaction products and mechanism of action, Biochemistry 12, 18–23PubMedCrossRefGoogle Scholar
  34. 34.
    Christeller JT (1981) The effect of bivalent cations on ribulose diphosphate carboxylase/oxygenase, Biochem J 193: 839–844PubMedGoogle Scholar
  35. 35.
    Mogel SN, McFadden BA (1990) Chemiluminescence of the Mn2+-activated ribulose-1,5-bisphosphate oxygenase reaction: evidence for singlet oxygen production, Biochemistry 29, 8333–8337PubMedCrossRefGoogle Scholar
  36. 36.
    Gailus V (1990) Vergleichende Untersuchungen an der Acetolactatsynthase aus höheren Pflanzen, Diplom Thesis, Universität Konstanz, Constance, GermanyGoogle Scholar
  37. 37.
    McCord JM, Fridovich I (1969) Superoxide dismutase an enzymic function for erythrocuprein (hemocuprein), J Biol Chem 244, 6049–6055PubMedGoogle Scholar
  38. 38.
    Corey EJ, Mehrotra MM, Khan AU (1987) Water induced dismutation of superoxide anion generates singlet molecular oxygen, Biochem Biophys Res Commun 145, 842–846PubMedCrossRefGoogle Scholar
  39. 39.
    Kanofsky J (1983) Singlet oxygen production by lactoperoxidase, J Biol Chem 258, 5991–5993PubMedGoogle Scholar
  40. 40.
    LaRossa RA, Van Dyk TK, Smulski DR (1990) A need for metabolic insulation: lessons from sulfonylurea genetics. In: Barak Z, Chipman DM, Schloss JV (eds) Biosynthesis of Branched Chain Amino Acids. VCH, Weinheim, pp 109–121Google Scholar
  41. 41.
    Van Dyk TK, LaRossa RA (1990) Prevention of endogenous 2-ketobutyrate toxicity in Salmonella typhimurium. In: Barak Z, Chipman DM, Schloss JV (eds) Biosynthesis of Branched Chain Amino Acids. VCH, Weinheim, pp 123–130Google Scholar
  42. 42.
    LaRossa RA, Van Dyk TK (1987) Metabolic mayhem caused by 2-ketoacid imbalances, Bioessays 7, 125–130PubMedCrossRefGoogle Scholar
  43. 43.
    LaRossa RA, Van Dyk TK, Smulski DR (1987) Toxic accumulation of α-ketobutyr- ate caused by inhibition of the branched-chain amino acid biosynthetic enzyme acetolactate synthase in Salmonella typhimurium, J Bacteriol 169, 1372–1378PubMedGoogle Scholar
  44. 44.
    Van Dyk TK, LaRossa RA (1986) Sensitivity of a Salmonella typhimurium AspC mutant to sulfometuron methyl, a potent inhibitor of acetolactate synthase II, J Bacteriol 165, 386–392PubMedGoogle Scholar
  45. 45.
    Van Dyk TK, LaRossa RA (1987) Involvement of ack-pta operon products in α- ketobutyrate metabolism by Salmonella typhimurium, Mol Gen Genet 207, 435–440PubMedCrossRefGoogle Scholar
  46. 46.
    Van Dyk TK, Smulski DR, Chang YY (1987) Pleiotropic effects of poxA regulatory mutations of Escherichia coli and Salmonella typhimurium, mutations conferring sulfometuron methyl and α-ketobutyrate hypersensitivity, J Bacteriol 169, 4540–4546PubMedGoogle Scholar
  47. 47.
    Epelbaum S, Landstein D, Arad S (M), Barak Z, Chipman DM, LaRossa RA, Van Dyk TK (1992) Is the inhibitory effect of the herbicide sulfometuron methyl due to 2-ketobutyrate accumulation. In: Singh BK, Flores HE, Shannon JC (eds) Biosynthesis and Molecular Regulation of Amino Acids in Plants. American Society of Plant Physiologists, Rockville, pp 352–353Google Scholar
  48. 48.
    Singh BK, Shaner DL (1992) Carbon flow through branched-chain amino acid biosynthetic pathway: lessons from acetohydroxy acid synthase inhibitors. In: Singh BK, Flores HE, Shannon JC (eds) Biosynthesis and Molecular Regulation of Amino Acids in Plants. American Society of Plant Physiologists, Rockville, pp 354–357Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1994

Authors and Affiliations

  • John V. Schloss
    • 1
  1. 1.Department of Medicinal ChemistryThe University of KansasLawrenceUSA

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