Elucidation of the methylerythritol phosphate pathway for isoprenoid biosynthesis in bacteria and plastids. A metabolic milestone achieved through genomics

Plant Physiology

Volumn 130, Issue 3, 2002, Pages 1079-1089

  Rodríguez Concepción, Manuel ^a   Boronat, Albert ^a  

^a UNIVERSITY OF BARCELONA   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 0036851226     PISSN: 00320889     EISSN: None     Source Type: Journal    
DOI: 10.1104/pp.007138     Document Type: Review

References (82)

1. Altincicek B, Kollas AK, Eberl M, Wiesner J, Sanderbrand S, Hintz M, Beck E, Jomaa H (2001a) LytB, a novel gene of the 2-C-methyl-D-erythritol 4-phosphate pathway of isoprenoid biosynthesis in Escherichia coli. FEBS Lett 499: 37-40
2. Altincicek B, Kollas AK, Sanderbrand S, Wiesner J, Hintz M, Beck E, Jomaa H (2001b) GcpE is involved in the 2-C-methyl-D-erythritol 4-phosphate pathway of isoprenoid biosynthesis in Escherichia coli. J Bacteriol 183: 2411-2416
3. Altincicek B, Moll J, Campos N, Foerster G, Beck E, Hoeffler JF, Grosdemange-Billiard C, Rodríguez-Concepciòn M, Rohmer M, Boronat A et al. (2001c) Human gamma-delta T cells are activated by intermediates of the 2-C-methyl-D-erythritol 4-phosphate pathway of isoprenoid biosynthesis. J Immunol 166: 3655-3658
4. Araki N, Kusumi K, Masamoto K, Niwa Y, Iba K (2000) Temperature-sensitive Arabidopsis mutant defective in 1-deoxy-D-xylulose 5-phosphate synthase within the plastid non-mevalonate pathway of isoprenoid biosynthesis. Physiol Plant 108: 19-24
5. Bouvier F, d'Harlingue A, Suire C, Backhaus RA, Camara B (1998) Dedicated roles of plastid transketolases during the early onset of isoprenoid biogenesis in pepper fruits. Plant Physiol 117: 1423-1431
6. Broers STJ (1994) Über die Frühen Stufen der Biosynthese von Isoprenoiden in Escherichia coli. PhD thesis. ETH Zürich, Switzerland
7. Budziszewski GJ, Lewis SP, Glover LW, Reineke J, Jones G, Ziemnik LS, Lonowski J, Nyfeler B, Aux G, Zhou Q et al. (2001) Arabidopsis genes essential for seedling viability: Isolation of insertional mutants and molecular cloning. Genetics 159: 1765-1778
8. Campos N, Rodríguez-Concepción M, Sauret-Güeto S, Gallego F, Lois LM, Boronat A (2001a) Escherichia coli engineered to synthesize isopentenyl diphosphate and dimethylallyl diphosphate from mevalonate: A novel system for genetic analysis of the 2-C-methyl-D-erythritol 4-phosphate pathway. Biochem J 353: 59-67
9. Campos N, Rodríguez-Concepción M, Seemann M, Rohmer M, Boronat A (2001b) Identification of gcpE as a novel gene of the 2-C-methyl-D-erythritol 4-phosphate pathway for isoprenoid biosynthesis in Escherichia coli. FEBS Lett 488: 170-173
10. Carretero-Paulet L, Ahumada I, Cunillera N, Rodríguez-Concepción M, Ferrer A, Boronat A, Campos N (2002) Expression and molecular analysis of the Arabidopsis thaliana DXR gene encoding 1-deoxy-D-xylulose 5-phosphate reductoisomerase, the first committed enzyme of the 2-C-methyl-D-erythritol 4-phosphate pathway. Plant Physiol 129: 1581-1591
11. Chahed K, Oudin A, Guivarch N, Hamdi S, Chénieux JH, Rideau M, Clastre M (2000) 1-Deoxy-D-xylulose 5-phosphate synthase from periwinkle: cDNA identification and induced gene expression in terpenoid indole alkaloid-producing cells. Plant Physiol Biochem 38: 559-566
12. Chappell J (1995) Biochemistry and molecular biology of the isoprenoid biosynthetic pathway in plants. Annu Rev Plant Physiol Plant Mol Biol 46: 521-547
13. Chappell J (2002) The genetics and molecular genetics of terpene and sterol origami. Curr Opin Plant Biol 5: 151-157
14. Charon L, Hoeffler JF, Pale-Grosdemange C, Lois LM, Campos N, Boronat A, Rohmer M (2000) Deuterium labeled isotopomers of 2-C-methyl-D-erythritol as tools for the elucidation of the 2-C-methyl-v-erythritol 4-phosphate (MEP) pathway for isoprenoid synthesis. Biochem J 346: 737-742
15. Croteau R, Kutchan TM, Lewis NG (2000) Natural products (secondary metabolites). In B Buchanan, W Gruissem, R Jones, eds, Biochemistry and Molecular Biology of Plants. American Society of Plant Biologists, Rockville, MD, pp 1250-1268
16. Cunningham FX, Lafond TP, Gantt E (2000) Evidence of a role for lytB in the nonmevalonate pathway of isoprenoid biosynthesis. J Bacteriol 182: 5841-5848
17. Duvold T, Calí P, Bravo JM, Rohmer M (1997) Incorporation of 2-C-methyl-D-erythritol, a putative isoprenoid precursor in the mevalonate-independent pathway, into ubiquinone and menaquinone of Escherichia coli. Tetrahedron Lett 38: 6181-6184
18. Eisenreich W, Rohdich F, Bacher A (2001) Deoxyxylulose phosphate pathway to terpenoids. Trends Plant Sci 6: 78-84
19. Eisenreich W, Schwarz M, Cartayrade A, Arigoni D, Zenk MH, Bacher A (1998) The deoxyxylulose phosphate pathway of terpenoid biosynthesis in plants and microorganisms. Chem Biol 5: R221-R233
20. Estévez JM, Cantero A, Reindl A, Reichler S, Leon P (2001) 1-Deoxy-D-xylulose-5-phosphate synthase, a limiting enzyme for plastidic isoprenoid biosynthesis in plants. J Biol Chem 25: 22901-22909
21. Estévez JM, Cantero A, Romero C, Kawaide H, Jimenez LF, Kuzuyama T, Seto H, Kamiya Y, Leon P (2000) Analysis of the expression of CLA1, a gene that encodes the 1-deoxyxylulose 5-phosphate synthase of the 2-C-methyl-D-erythritol-4-phosphate pathway in Arabidopsis. Plant Physiol 124: 95-103
22. Flesch G, Rohmer M (1988) Prokaryotic hopanoids: The biosynthesis of the bacteriohopan skeleton. Eur J Biochem 175: 405-411
23. Fray RG, Wallace A, Fraser PD, Valero D, Hedden P, Bramley PM, Grierson D (1995) Constitutive expression of a fruit phytoene synthase gene in transgenic tomatoes causes dwarfism by redirecting metabolites from the gibberellin pathway. Plant J 8: 693-701
24. Giner JL, Jaun B, Arigoni B (1998) Biosynthesis of isoprenoids in Escherichia coli: The fate of the 3-H and 4-H atoms of 1-deoxy-D-xylulose. J Chem Soc Chem Commun 17: 1857-1858
25. Hahn FM, Hurlburt AP, Poulter CD (1999) Escherichia coli open reading frame 696 is idi, a nonessential gene encoding isopentenyl diphosphate isomerase. J Bacteriol 181: 4499-4504
26. Harker M, Bramley PM (1999) Expression of procaryotic 1-deoxy-D-xylulose 5-phosphatases in Escherichia coli increases carotenoid and ubiquinone biosynthesis. FEBS Lett 448: 115-119
27. Hecht S, Eisenreich W, Adam P, Amslinger S, Kis K, Bacher A, Arigoni D, Rohdich F (2001) Studies on the nonmevalonate pathway to terpenes: The role of the GcpE (IspG) protein. Proc Natl Acad Sci USA 26: 14837-14842
28. Herz S, Wungsintaweekul J, Schuhr CA, Hecht S, Lüttgen H, Sagner S, Fellermeier M, Eisenreich W, Zenk MH, Bacher A, Rohdich F (2000) Biosynthesis of terpenoids: YgbB protein converts 4-diphosphocytidyl-2C-methyl-D-erythritol 2-phosphate to 2C-methyl-D-erythritol 2,4-cyclodiphosphate. Proc Natl Acad Sci USA 97: 2486-2490
29. Hintz M, Reichenberg A, Altincicek B, Bahr U, Gschwind RM, Kollas AK, Beck E, Wiesner J, Eberl M, Jomaa H (2001) Identification of (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate as a major activator for human T cells in Escherichia coli. FEBS Lett 509: 317-322
30. Jomaa H, Wiesner J, Sanderbrand S, Altincicek B, Weidemeyer K, Hintz M, Türbachova I, Eberl M, Zeidler J, Lichtenthaler HK et al. (1999) Inhibitors of the nonmevalonate pathway of isoprenoid biosynthesis as antimalarial drugs. Science 285: 1573-1576
31. Kemp LE, Bond CS, Hunter WN (2001) Crystallization and preliminary x-ray diffraction studies of recombinant Escherichia coli 4-diphosphocytidyl-2-C-methyl-D-erythritol synthetase. Acta Crystallogr D Biol Crystallogr 57: 1189-1191
32. Kemp LE, Bond CS, Hunter WN (2002) Structure of 2C-methyl-D-erythritol 2,4-cyclodiphosphate synthase: An essential enzyme for isoprenoid biosynthesis and target for antimicrobial drug development. Proc Natl Acad Sci USA 99: 6591-6596
33. Kuzuyama T, Takagi M, Kaneda K, Dairi T, Seto H (2000a) Formation of 4-(cytidine 5′-diphospho)-2-C-methyl-D-erythritol from 2-C-methyl-D-erythritol 4-phosphate by 2-C-methyl-D-erythritol 4-phosphate cytidylyl-transferase, a new enzyme in the nonmevalonate pathway. Tetrahedron Lett 41: 703-706
34. Kuzuyama T, Takagi M, Kaneda K, Watanabe H, Dairi T, Seto H (2000b) Studies on the nonmevalonate pathway: Conversion of 4-(cytidine 5′-diphospho)-2-C-methyl-D-erythritol to its 2-phospho derivative by 4-(cytidine 5′-diphospho)-2-C-methyl-D-erythritol kinase. Tetrahedron Lett 41: 2925-2928
35. Kuzuyama T, Takagi M, Takahashi S, Seto H (2000c) Cloning and characterization of 1-deoxy-D-xylulose 5-phosphate synthase from Streptomyces sp. strain CL190, which uses both the mevalonate and nonmevalonate pathways for isopentenyl diphosphate biosynthesis. J Bacteriol 182: 891-897
36. Kuzuyama T, Takahashi S, Watanabe H, Seto H (1998) Direct formation of 2-C-methyl-D-erythritol 4-phosphate from 1-deoxy-D-xylulose 5-phosphate by 1-deoxy-D-xylulose 5-phosphate reductoisomerase, a new enzyme in the non-mevalonate pathway to isopentenyl diphosphate. Tetrahedron Lett 39: 4509-4512
37. Lange BM, Croteau R (1999a) Isopentenyl diphosphate biosynthesis via a mevalonate-independent pathway: Isopentenyl monophosphate kinase catalyzes the terminal enzymatic step. Proc Natl Acad Sci USA 96: 13714-13719
38. Lange BM, Croteau R (1999b) Isoprenoid biosynthesis via a mevalonate-independent pathway in plants: Cloning and heterologous expression of 1-deoxy-D-xylulose 5-phosphate reductoisomerase from peppermint. Arch Biochem Biophys 365: 170-174
39. Lange BM, Ketchum REB, Croteau R (2001) Isoprenoid biosynthesis: Metabolite profiling of peppermint oil gland secretory cells and application to herbicide target analysis. Plant Physiol 127: 305-314
40. Lange BM, Wildung MR, McCaskill D, Croteau R (1998) A family of transketolases that directs isoprenoid biosynthesis via a mevalonate-independent pathway. Proc Natl Acad Sci USA 95: 2100-2104
41. Lichtenthaler HK (1999) The 1-deoxy-D-xylulose 5-phosphate pathway of isoprenoid biosynthesis in plants. Annu Rev Plant Physiol Plant Mol Biol 50: 47-65
42. Lichtenthaler HK, Rohmer M, Schwender J (1997) Two independent biochemical pathways for isopentenyl diphosphate and isoprenoid biosynthesis in higher plants. Physiol Plant 101: 643-652
43. Lois LM, Campos N, Rosa Putra S, Danielsen K, Rohmer M, Boronat A (1998) Cloning and characterization of a gene from Escherichia coli encoding a transketolase-like enzyme that catalyzes the synthesis of D-1-deoxyxylulose 5-phosphate, a common precursor for isoprenoid, thiamin, and pyridoxol biosynthesis. Proc Natl Acad Sci USA 95: 2105-2110
44. Lois LM, Rodríguez-Concepción M, Gallego F, Campos N, Boronat A (2000) Carotenoid biosynthesis during tomato fruit development: Regulatory role of 1-deoxy-D-xylulose 5-phosphate synthase. Plant J 22: 503-513
45. Lüttgen H, Rohdich F, Herz S, Wungsintaweekul J, Hecht S, Schuhr CA, Fellermeier M, Sagner S, Zenk MH, Bacher A et al. (2000) Biosynthesis of terpenoids: YchB protein of Escherichia coli phosphorylates the 2-hydroxy group of 4-diphosphocytidyl-2-C-methyl-D-erythritol. Proc Natl Acad Sci USA 97: 1062-1067
46. Mahmoud SS, Croteau RB (2001) Metabolic engineering of essential oil yield and composition in mint by altering expression of deoxyxylulose phosphate reductoisomerase and menthofuran synthase. Proc Natl Acad Sci USA 98: 8915-8920
47. Mandel MA, Feldmann KA, Herrera-Estrella L, Rocha-Sosa M, León P (1996) CLA1, a novel gene required for chloroplast development, is highly conserved in evolution. Plant J 9: 649-658
48. Matthews PD, Wurtzel ET (2000) Metabolic engineering of carotenoid accumulation in Escherichia coli by modulation of the isoprenoid precursor pool with expression of deoxyxylulose phosphate synthase. Appl Microbiol Biotechnol 53: 396-400
49. McGarvey DJ, Croteau R (1995) Terpenoid metabolism. Plant Cell 7: 1015-1026
50. Miller B, Heuser T, Zimmer W (1999) A Synechococcus leopotiensis SAUG 1402-1 operon harboring the 1-deoxyxylulose 5-phosphate synthase gene and two additional open reading frames is functionally involved in the dimethylallyl diphosphate synthesis. FEBS Lett 460: 485-490
51. Miller B, Heuser T, Zimmer W (2000) Functional involvement of a deoxy-D-xylulose 5-phosphate reductoisomerase gene harboring locus of Synechococcus leopoliensis in isoprenoid biosynthesis. FEBS Lett 481: 221-226
52. Okada K, Kawaide H, Kuzuyama T, Seto H, Curtis IS, Kamiya Y (2002) Antisense and chemical suppression of the nonmevalonate pathway affects ent-kaurene biosynthesis in Arabidopsis. Planta 215: 339-344
53. Querol J, Campos N, Imperial S, Boronat A, Rodríguez-Concepción M (2002) Functional analysis of the Arabidopsis thaliana GCPE protein involved in plastid isoprenoid biosynthesis. FEBS Lett 514: 343-346
54. Querol J, Rodríguez-Concepción M, Boronat A, Imperial S (2001) Essential role of residue H49 for activity of Escherichia coli 1-deoxy-D-xylulose 5-phosphate synthase, the enzyme catalyzing the first step of the 2-C-methyl-D-erythritol 4-phosphate pathway for isoprenoid biosynthesis. Biochem Biophys Res Commun 289: 155-160
55. Reuter K, Sanderbrand S, Jomaa H, Wiesner J, Steinbrecher I, Beck E, Hintz M, Klebe G, Stubbs MT (2002) Crystal structure of 1-deoxy-D-xylulose-5-phosphate reductoisomerase, a crucial enzyme in the nonmevalonate pathway of isoprenoid biosynthesis. J Biol Chem 277: 5378-5384
56. Richard SB, Bowman ME, Kwiatkowski W, Kang I, Chow C, Lillo AM, Cane DE, Noel JP (2001) Structure of 4-diphosphocytidyl-2-C-methylerythritol synthetase involved in mevalonate-independent isoprenoid biosynthesis. Nat Struct Biol 8: 641-648
57. Richard SB, Ferrer JL, Bowman ME, Lillo AM, Tetzlaff CN, Cane DE, Noel JP (2002) Structure and mechanism of 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase: An enzyme in the mevalonate-independent isoprenoid biosynthetic pathway. J Biol Chem 277: 8667-8672
58. Rodríguez-Concepción M, Ahumada I, Diez-Juez E, Sauret-Güeto S, Lois LM, Gallego F, Carretero-Paulet L, Campos N, Boronat A (2001) 1-Deoxy-D-xylulose 5-phosphate reductoisomerase and plastid isoprenoid biosynthesis during tomato fruit ripening. Plant J 27: 213-222
59. Rodríguez-Concepción M, Campos N, Lois LM, Maldonado C, Hoeffler JF, Grosdemange-Billiard C, Rohmer M, Boronat A (2000) Genetic evidence of branching in the isoprenoid pathway for the production of isopentenyl diphosphate and dimethylallyl diphosphate in Escherichia coli. FEBS Lett 473: 328-332
60. Rodríguez-Concepción M, Gruissem W (1999) Arachidonic acid alters tomato HMG expression and fruit growth and induces 3-hydroxy-3-methylglutaryl coenzyme A reductase-independent lycopene accumulation. Plant Physiol 119: 41-48
61. Rohdich F, Hecht S, Gärtner K, Adam P, Krieger C, Amslinger S, Arigoni D, Bacher A, Eisenreich W (2002) Studies on the nonmevalonate terpene biosynthetic pathway: Metabolic role of IspH (LytB) protein. Proc Natl Acad Sci USA 99: 1158-1163
62. Rohdich F, Wungsintaweekul J, Eisenreich W, Richter G, Schuhr CA, Hecht S, Zenk MH, Bacher A (2000b) Biosynthesis of terpenoids: 4-diphosphocytidyl-2-C-methyl-D-erythritol synthase of Arabidopsis thaliana. Proc Natl Acad Sci USA 97: 6451-6456
63. Rohdich F, Wungsintaweekul J, Fellermeier M, Sagner S, Herz S, Kis K, Eisenreich W, Bacher A, Zenk MH (1999) Cytidine 5′-triphosphate-dependent biosynthesis of isoprenoids: YgbP protein of Escherichia coli catalyzes the formation of 4-diphosphocytidyl-2-C-methylerythritol. Proc Natl Acad Sci USA 96: 11758-11763
64. Rohdich F, Wungsintaweekul J, Lüttgen H, Fischer M, Eisenreich W, Schuhr CA, Fellermeier M, Schramek N, Zenk MH, Bacher A (2000a) Biosynthesis of terpenoids: 4-diphosphocytidyl-2-C-methyl-D-erythritol kinase from tomato. Proc Natl Acad Sci USA 97: 8251-8256
65. Rohmer M (1999) The discovery of a mevalonate-independent pathway for isoprenoid biosynthesis in bacteria, algae and higher plants. Nar Prod Rep 16: 565-574
66. Rohmer M, Knani M, Simonin P, Sutter B, Sahm H (1993) Isoprenoid biosynthesis in bacteria: A novel pathway for early steps leading to isopentenyl diphosphate. Biochem J 295: 517-524
67. Rohmer M, Seemann M, Horbach S, Bringer-Meyer S, Sahm H (1996) Glyceraldehyde 3-phosphate and pyruvate as precursors of isoprenic units in an alternative non-mevalonate pathway for terpenoid biosynthesis. J Am Chem Soc 118: 2564-2566
68. Schindler S, Bach TJ, Lichtenthaler HK (1985) Differential inhibition by mevinolin of prenyllipid accumulation in radish seedlings. Z Naturforsch 40c: 208-214
69. Schwarz MK (1994) Terpen Biosynthese in Ginkgo biloba: Eine Überraschende Geschichte. PhD thesis. ETH Zürich, Switzerland
70. Schwender J, Müller C, Zeidler J, Lichtenthaler HK (1999) Cloning and heterologous expression of a cDNA encoding 1-deoxy-v-xylulose 5-phosphate reductoisomerase of Arabidopsis thaliana. FEBS Lett 455: 140-144
71. Seemann M, Campos N, Rodríguez-Concepción M, Ibáñez E, Duvold T, Tritsch D, Boronat A, Rohmer M (2002b) Isoprenoid biosynthesis in Escherichia coli via the methylerythritol phosphate pathway: Enzymatic conversion of methylerythritol cyclodiphosphate into a phosphorylated derivative of (E)-2-methylbut-2-ene-1,4-diol. Tetrahedron Lett 43: 1413-1415
72. Seemann M, Hoeffler JF, Grosdemange-Billiard C, Campos N, Rodríguez-Concepción M, Boronat A, Rohmer M (2002a) Isoprenoid biosynthesis via the methylerythritol phosphate pathway: 2-C-methyl-D-erythritol 2,4-cyclodiphosphate as putative substrate of the gcpE gene product in Escherichia coli. Tetrahedron Lett 43: 775-778
73. Sprenger GA, Schorken U, Wiegert T, Grolle S, de Graaf AA, Taylor SV, Begley TP, Bringer-Meyer S, Sahm H (1997) Identification of a thiamin-dependent synthase in Escherichia coli required for the formation of the 1-deoxy-D-xylulose 5-phosphate precursor to isoprenoids, thiamin, and pyridoxol. Proc Natl Acad Sci USA 94: 12857-12862
74. Steinbacher S, Kaiser J, Wungsintaweekul J, Hecht S, Eisenreich W, Gerhardt S, Bacher A, Rohdich F (2002) Structure of 2-C-methyl-D-erythritol-2,4-cyclodiphosphate synthase involved in mevalonate-independent biosynthesis of isoprenoids. J Mol Biol 316: 79-88
75. Takagi M, Kuzuyama T, Kazuhide K, Watanabe H, Dairi T, Seto H (2000) Studies on the nonmevalonate pathway: Formation of 2-C-methyl-D-erythritol 2,4-cyclodiphosphate from 2-phospho-4-(cytidine 5′-diphospho)-2-C-methyl-D-erythritol. Tetrahedron Lett 41: 3395-3398
76. Takahashi S, Kuzuyama T, Watanabe H, Seto H (1998) A 1-deoxy-D-xylulose 5-phosphate reductoisomerase catalyzing the formation of 2-C-methyl-D-erythritol 4-phosphate in an alternative nonmevalonate pathway for terpenoid biosynthesis. Proc Natl Acad Sci USA 95: 9879-9884
77. Veau B, Oudin A, Chénieux JC, Rideau M, Clastre M (2000) Cloning and expression of cDNAs encoding two enzymes of the MEP pathway in Catharanthus roseus. Biochim Biophys Acta 1517: 159-163
78. Walter MH, Fester T, Strack D (2000) Arbuscular mycorrhizal fungi induce the non-mevalonate methylerythritol phosphate pathway of isoprenoid biosynthesis correlated with accumulation of the "yellow pigment" and other apocarotenoids. Plant J 21: 571-578
79. Wolff M, Seemann M, Grosdmange-Billiard C, Tritsch D, Campos N, Rodríguez-Concepción M, Boronat A, Rohmer M (2002) Isoprenoid biosynthesis via the methylerythritol phosphate pathway. (E)-4-Hydroxy-3-methyl but-2-enyl diphosphate: Chemical synthesis and formation from methylerythritol cyclodiphosphate by a cell-free system from Escherichia coli. Tetrahedron Lett 43: 2555-2559
80. Yajima S, Nonaka T, Kuzuyama T, Seto H, Ohsawa K (2002) Crystal structure of 1-deoxy-D-xylulose 5-Phosphate reductoisomerase complexed with cofactors: Implications of a flexible loop movement upon substrate binding. J Biochem 131: 313-317
81. Zeidler J, Schwender J, Müller C, Lichtenthaler HK (2000) The nonmevalonate isoprenoid biosynthesis of plants as a test system for drugs against malaria and pathogenic bacteria. Biochem Soc Trans 28: 796-798
82. Zeidler J, Schwender J, Müller C, Wiesner J, Weidemeyer C, Beck E, Jomaa H, Lichtenthaler HK (1998) Inhibition of the non-mevalonate 1-deoxy-D-xylulose-5-phosphate pathway of plant isoprenoid biosynthesis by fosmidomycin. Z Naturforsch 53c: 980-986