Amino acid activation and polymerization at modular multienzymes in nonribosomal peptide biosynthesis

Amino Acids

Volumn 10, Issue 3, 1996, Pages 201-227

  Stein, T ^a   Vater, J ^a  

^a TECHNISCHE UNIVERSITÄT BERLIN   (Germany)

Author keywords

Amino acid activation; Amino acids; Aminoacyl adenylation; Modular structure; Multienzymes; Multiple 4' phosphopantetheine cofactors; Nonribosomal peptide biosynthesis; Peptide antibiotics

Indexed keywords

AMINO ACID; MICROBIAL ENZYME; PEPTIDE SYNTHASE;

CYCLIZATION; ENZYME ACTIVITY; ENZYME STRUCTURE; METHYLATION; NONHUMAN; POLYMERIZATION; PRIORITY JOURNAL; PROTEIN SYNTHESIS; REVIEW; RNA TRANSLATION;

EID: 0029896295     PISSN: 09394451     EISSN: None     Source Type: Journal    
DOI: 10.1007/BF00807324     Document Type: Review

References (132)

1. Aharonowitz Y, Bergmeyer J, Cantoral JM, Cohen G, Demain AL, Fink U, Kinghorn J, Kleinkauf H, MacCabe A, Palissa H, Pfeifer E, Schwecke T, van Liempt H, von Döhren H, Wolfe S, Zhang J (1993) δ-(L-α-Aminoadipyl)-L-cysteinyl-D-valine synthetase, the multienzyme integrating the four primary reactions in β-lactam biosynthsis, as a model peptide synthetase. Biotechnology 11: 807-810
2. Alvarez E, Meesschaert B, Montenegro E, Gutiérrez S, Díez B, Barredo JL, Martín JF (1993) The isopenicillin-N acyltransferase of Penicillium chrysogenum has isopenicillin-N-amidohydrolase, 6-aminopenicillanic acid acyltransferase and penicillin amidase activities, all of which encoded by the single penDE gene. Eur J Biochem 215: 323-332
3. Babbitt PC, Kenyon GL, Martin BM, Charest H, Slyvestre M, Scholten JD, Chang K-H, Liang P-H, Dunaway-Mariano D (1992) Ancestry of the 4-chlorobenzoate dehalogenase: analysis of amino acid sequence identities among families of acyl : adenyl ligases, enoyl-CoA hydratases/isomerases, and acyl-CoA thioesterases. Biochemistry 31: 5594-5604
4. Babbitt PC, Mrachko GT, Hasson MS, Huisman GW, Kolter R, Ringe D, Petsko GA, Kenyon GL, Gerlt JA (1995) A functionally diverse enzyme superfamily that abstracts the α-protons of carboxylic acids. Science 267: 1159-1161
5. Becker-André M, Schulze-Lefert P, Hahlbrock K (1991) Structural comparison, modes of expression, and putative cis-acting elements of the two 4-coumarate : CoA ligase genes in potato. J Biol Chem 266: 8551-8559
6. Bevitt DJ, Cortes J, Haydock SF, Leadlay PF (1992) 6-Deoxyerythronolide-B synthetase 2 from Saccharopolyspora erythraea. Eur J Biochem 204: 39-49
7. Bibb MJ, Cohen SN (1982) Gene expression in streptomyces: construction and application of promoter-probe plasmid vectors in Streptomyces lividans. Mol Gen Genet 187: 265-277
8. Billich A, Zocher R (1987) N-Methyltransferase function of the multifunctional enzyme enniatin synthetase. Biochemistry 26: 8417-8423
9. Brick P, Blow DM (1987) Crystal structure of a deletion mutant of a tyrosine-tRNA synthetase complexed with tyrosine. J Mol Biol 194: 407-17
10. Brick P, Bhat TH, Blow DM (1989) Structure of tyrosyl-tRNA synthetase refined at 2.3. Å resolution. Interaction of the enzyme with the tyrosyl adenylate. J Mol Biol 208:83-98
11. Brenner S (1988) The molecular evolution of genes and proteins: a tale of two serines. Nature 334: 528-530
12. Burbaum JJ, Schimmel P (1991) Structural relationships and the classification of aminoacyl-tRNA synthetases. J Biol Chem 266: 16965-16968
13. Carter CW Jr (1993) Cognition, mechanism, and evolutionary relationships in aminoacyl-tRNA synthetases. Annu Rev Biochem 62: 715-748
14. Choughuley ASU, Lemmon RM (1966) Production of cysteic acid, taurine and cysteamine under primitive earth conditions. Nature 210: 628-629
15. Coque JJR, Martín JF, Calzada JG, Liras P (1991) The cephamycin biosynthetic genes pcbAB, encoding a large multidomain peptide synthetase, and pcbC of Nocardia lactamdurans are clustered together in an organization different from the same genes in Acremonium chrysogenum and Penicillium chrysogenum. Mol Microbiol 5: 1125-1133
16. Cortes J, Haydock SF, Roberts GA, Bevitt DJ, Leadley PF (1990) An unusually large multifunctional polypeptide in the erythromycin-producing polyketide synthase of Saccharopolyspora erythraea. Nature 348: 176-178
17. Cortes J, Wiesmann KEH, Roberts GA, Brown MJB, Staunton J, Leadley PF (1995) Repositioning of a domain in a modular polyketide synthase to promote specific chain cleavage. Science 268: 1487-1489
18. Cosmina P, Rodriguez F, Ferra FD, Grandi G, Perego M, Venema G, van Sinderen D (1993) Sequence and analysis of the genetic locus responsible for surfactin synthesis in Bacillus subtilis. Mol Microbiol 8: 821-831
19. Davis CB, Smith KE, Campbell BN Jr, Hammes GG (1990) The ATP binding site of the Yeast plasma membrane proton-translocating ATPase. J Biol Chem 265: 1300-1305
20. Debellé F, Sharma SB (1986) Nucleotide sequence of Rhizobium meliloti RCR2011 genes involved in host specificity of nodulation. Nucleic Acids Res 14: 7453-7472
21. De Crécy-Lagard V, Marlière P, Saurin W (1995) Multienzymatic non ribosomal peptide biosynthesis: identification of the functional domains catalysing peptide elongation and epimerisation. C R Acad Sci Paris. Life Sci 318: 927-936
22. de Duve C (1987) Selection by differential molecular survival: a possible mechanism of early chemical evolution. Proc Natl Acad Sci USA 84: 8253-8256
23. de Duve C (1991) Blueprint for a cell: the nature and origin of life. N Patterson Publishers, Burlington New York
24. de Prat Gay G, Duckworth HW, Fersht AR (1993) Modification of the amino acid specificity of tyrosyl-tRNA synthetase by protein engineering. FEBS Lett 318: 167-171
25. Dieckmann R, Lee Y-O, van Liempt H, von Döhren H, Kleinkauf H (1995) Expression of an active adenylate-forming domain of peptide synthetases corresponding to acyl-CoA-synthetases. FEBS Lett 357: 212-216
26. Díez B, Gutiérrez S, Barredo JL, van Solingen P, van der Voort LHM, Martín JF (1990) The cluster of penicillin biosynthetic genes. Identification and characterization of the pcbAB gene encoding the α-aminoadipyl-cysteinyl-valine synthetase and linkage to the pcbC and penDE genes. J Biol Chem 265: 16358-16365
27. Dittmann J, Wenger RM, Kleinkauf H, Lawen A (1994) Mechanism of cyclosporin A biosynthesis. Evidence for synthesis via a single linear undecapeptide precursor. J Biol Chem 269: 2841-2846
28. Donadio S, Staver MJ, McAlpine JB, Swanson SJ, Katz L (1991) Modular organization of genes required for complex polyketide biosynthesis. Science 252: 675-679
29. Eriani G, Delarue M, Poch O, Gangloff J, Moras D (1990) Partition of tRNA synthetases into two classes based on mutually exclusive ests of sequence motifs. Nature 347: 203-206
30. Fan C, Moews PC, Shi Y, Walsh CT, Knox JR (1995) A common fold for peptide synthetases cleaving ATP to ADP: glutathione synthetase and D-alanine:D-alanine ligase of Escherichia coli. Proc Natl Acad Sci USA 92: 1172-1176
31. Fernández-Moreno MA, Martínez E, Boto L, Hopwood DA, Malpartida F (1992) Nucleotide sequence and deduced functions of a set of cotranscribed genes of Streptomyces coelicolor A32 including the polyketide synthase for the antibiotic actinorhodin. J Biol Chem 267: 19278-19290
32. Fulda M, Heinz E, Wolter FP (1994) The fadD gene of Escherichia coli K12 is located close to rnd at 39.6 min of the chromosomal map and is a new member of the AMP-binding protein family. Mol Gen Genet 242: 241-249
33. Fuma S, Fujishima Y, Corbell N, D'Souza C, Nakano MM, Zuber P, Yamane K (1993) Nucleotide sequence of 5′ portion of srfA that contains the region required for competence establishement in Bacillus subtilis. Nucleic Acids Res 21: 93-97
34. Galli G, Rodriguez F, Cosmina P, Pratesi C, Nogarotto R, de Ferra F, Grandi G (1994) Characterization of the surfactin synthetase multi-enzyme complex. Biochim Biophys Acta 1205: 19-28
35. Gerlt JA, Gassman PG (1993) Understanding the rates of certain enzyme-catalyzed reactions: proton abstraction from carbon acids, acyl-transfer reactions, and displacement of phosphodiesters. Biochemistry 32: 11943-11952
36. Gocht M, Marahiel MA (1994) Analysis of core sequences in the D-Phe activating domain of the multifunctional peptide synthetase TycA by site directed mutagenesis. J Bacteriol 176: 2654-2662
37. Gutiérrez S, Díez B, Montenegro E, Martín JF (1991) Characterization of the Cephalosporium acremonium pcbAB gene encoding α-aminoadipyl-cysteinyl-valine synthetase, a large multidomain peptide synthetase: linkage to the pcbC gene as a cluster of early cephalosporin biosynthetic genes and evidence of multiple functional domains. J Bacteriol 173: 2354-2365
38. Haese A, Schubert M, Herrmann M, Zocher R (1993) Molecular characterization of the enniatin synthetase gene encoding a multifunctional enzyme catalysing N-methyldepsipeptide formation in Fusarium scirpi. Mol Microbiol 7: 905-914
39. Hale RS, Jordan KN, Leadlay PF (1987) A small, discrete acyl carrier protein is involved in de novo fatty acid biosynthesis in Streptomyces erythraeus. FEBS Lett 224: 133-136
40. Hanks SH, Quinn AM, Hunter T (1988) The protein kinase family: conserved features and deduced phylogeny of the catalytic domains. Science 241: 42-52
41. Hawkins AR, Lamb HK (1995) The molecular biology of multidomain proteins. Eur J Biochem 232: 7-18
42. Higgins CF, Hiles ID, Salmond GPC, Gill DR, A Downie J, Evans IJ, Holland IB, Gray L, Buckel SD, Bell AW, Hermodson MA (1986) A family of related ATP-binding subunits coupled to many distinct biological processes in bacteria. Nature 323: 448-450
43. Hoffmann K, Schneider-Scherzer E, Kleinkauf H, Zocher R (1994) Purification and characterization of eucaryotic alanine racemase acting as key enzyme in cyclosporin biosynthesis. J Biol Chem 269: 12710-12714
44. Holak TA, Kearsley SK, Kim Y, Prestegard JH (1988) Three-dimensional structure of acyl carrier protein determined by NMR pseudoenergy and distance geometry calculations. Biochemistry 27: 6135-6142
45. Holak T, Nilges M, Prestegard JH, Gronenborn AM, Clore GM (1988) Three-dimensional structure of acyl carrier protein in solution determined by nuclear magnetic, resonance and the combined use of dynamical simulated annealing and distance geometry. Eur J Biochem 175: 9-15
46. Hori K, Yamamoto Y, Minetoki T, Kurotsu T, Kanda M, Miura S, Okamura K, Furuyama J, Saito Y (1989) Molecular cloning and nucleotide sequence of the gramicidin S synthetase 1 gene. J Biochem (Tokyo) 106: 639-645
47. Huang C-S, Anderson ME, Meister A (1993) Amino acid sequence and function of the light subunit of rat kidney γ-glutamylcysteine synthetase. J Biol Chem 268: 20578-20583
48. Kanda M, Hori K, Kurotsu T, Miura S, Saito Y (1989) Reaction mechanism of gramicidin S synthetase 1, phenylalanine racemase, of Bacillus brevis. J Biochem (Tokyo) 105: 653-659
49. Keefe AD, Newton GL, Miller SL (1995) A possible prebiotic synthesis of pantetheine, a pecursor to coenzyme A. Nature 373: 683-685
50. Kleinkauf H, von Döhren H (1990a) Nonribosomal biosynthesis of peptide antibiotics. Eur J Biochem 192: 1-15
51. Kleinkauf H, von Döhren H (1990b) Bioactive peptide analogs: in vivo and in vitro production. Progr Drug Res 34: 287-317
52. Kleinkauf H, Roskoski jr R, Lipmann F (1971) Pantetheine-linked peptide intermediates in gramicidin S and tyrocidine biosynthesis. Proc Natl Acad Sci USA 68: 2069-2072
53. Krätzschmar J, Krause M, Marahiel MA (1989) Gramicidin S biosynthesis operon containing the structural genes grsA and grsB has an open reading frame encoding a protein homologous to fatty acid thioesterases. J Bacteriol 171: 5422-5429
54. Kuo TM, Ohlrogge JB (1984) The primary structure of spinach acylcarrier protein. Arch Biochem Biophys 234: 290-296
55. Kurahashi K (1974) Biosynthesis of small peptides. Annu Rev Biochem 43: 445-459
56. Kurotsu T, Hori K, Saito Y (1991) Characterization and location of the L-proline activating fragment from the multifunctional gramicidin S synthetase 2. J Biochem (Tokyo) 109: 763-769
57. Laland SG, Zimmer T-L (1973) The protein thiotemplate mechanism of synthesis for the peptide antibiotics produced by Bacillus brevis. Essays Biochem 9: 31-57
58. Landro JA, Gerlt JA, Kozarich KW, Koo CW, Shah VJ, Kenyon GL, Neidhart DJ, Fujita S, Petsko GA (1994) The role of lysine 166 in the mechanism of mandelate racemase from Pseudomonas putida: mechanistic and crystallographic evidence for stereospecific alkylation by (R)-α-phenylglycidate. Biochemistry 33: 635-643
59. Lawen A, Zocher R (1990) Cyclosporin synthetase: the most complex synthesizing multienzyme polypeptide so far described. J Biol Chem 265: 11355-11360
60. Lee SG, Lipmann F (1974) Isolation of a peptidyl-pantetheine-protein from tyrocidine-synthesizing polyenzyme. Proc Natl Acad Sci USA 71: 607-611
61. Liaw S-H, Eisenberg D (1994) Structural model for the reaction mechanism of glutamine synthetase, based on five crystal structures of enzyme-substrate complexes. Biochemistry 33: 675-681
62. Lipmann F (1954) In: Mc Elroy WD, Glass B (eds) The mechanism of enzyme action. John Hopkins University Press, Baltimore, p 599
63. Lipmann F (1965) Projecting backward from the present stage of evolution of biosynthesis. In: Fox SW (ed) The origins of prebiological systems. Academic Press, New York, pp 259-273
64. Lipmann F (1973) Nonribosomal polypeptide synthesis on polyenzyme templates. Accts Chem Res 6: 361-367
65. MacCabe AP, van Liempt H, Palissa H, Unkles SE, Riach MBR, Pfeifer E, von Döhren H, Kinghorn J (1991) δ-(L-α-Aminoadipyl)-L-cysteinyl-D-valine synthetase from Aspergillus nidulans. Molecular characterization of the acvA gene encoding the first enzyme of the penicillin biosynthetic pathway. J Biol Chem 266: 12646-12654
66. Marahiel MA (1992) Multidomain enzymes involved in peptide synthesis. FEBS Lett 307: 40-43
67. McDaniel R, Ebert-Khosla S, Hopwood DA, Khosla C (1993) Engineered biosynthesis of novel polyketides. Science 262: 1546-1550
68. McDaniel R, Ebert-Khosla S, Hopwood DA, Khosla C (1995) Rational design of aromatic polyketide natural products by recombinant assembly of enzymatic subunits. Nature 375: 549-554
69. Meister A (1988) Glutathione metabolism and its selective modification. J Biol Chem 263: 17205-17208
70. Menkhaus M, Ullrich C, Kluge B, Vater J, Vollenbroich D, Kamp RM (1993) Structural and functional organization of the surfactin synthetase multienzyme system. J Biol Chem 268: 7678-7684
71. Miller SL (1953) A production of amino acids under possible primitive earth conditions. Science 117: 528-529
72. Miller SL, Schlesinger G (1993a) Prebiotic syntheses of vitamin coenzymes: I. Cysteamine and 2-mercaptoethanesulfonic acid (coenzyme M). J Mol Evol 36: 302-307
73. Miller SL, Schlesinger G (1993b) Prebiotic syntheses of vitamin coenzymes: II. Pantoic acid, pantothenic acid, and the composition of coenzyme A. J Mol Evol 36: 308-314
74. Miller SL, Urey HC (1959) Organic compound synthesis on the primitive earth. Science 130: 245-251
75. Mirande M (1991) Aminoacyl-tRNA synthetase family from procaryotes and eucaryotes: structural domains and their implications. Prog Nucleic Acid Res 40: 95-142
76. Moras D (1992) Structural and functional relationships between aminoacyl-tRNA synthetases. TIBS 17: 159-164
77. Neidhart DJ, Howell PL, Petsko GA, Powers VM, Li R, Kenyon GL, Gerlt JA (1991) Mechanism of the reaction catalyzed by mandelate racemase. 2. Crystal structure of mandelate racemase at 2.5-Å resolution: identification of the active site and possible catalytic residues. Biochemistry 30: 9264-9273
78. Osterberg R, Orgel LE (1972) Polyphosphate and trimetaphosphate formation under potentially prebiotic conditions. J Molec Evol 1: 241-248
79. Pavela-Vrancic M, Pfeifer E, Schröder W, von Döhren H, Kleinkauf H (1994a) Identification of the ATP binding site in tyrocidine synthetase 1 by selective modification with fluorescein 5′-isothiocyanate. J Biol Chem 269: 14962-14966
80. Pavela-Vrancic M, Pfeifer E, van Liempt H, Schäfer H-J, von Döhren H, Kleinkauf H (1994b) ATP binding in peptide synthetases: determination of contact sites of the adenine moiety by photoaffinity labeling of tyrocidine synthetase 1 with 2-azidoadenosine triphosphate Biochemistry 33: 6276-6283
81. Pavela-Vrancic M, van Liempt H, Pfeifer E, Freist W, von Döhren H (1994c) Nucleotide binding by multienzyme peptide synthetases. Eur J Biochem 220: 535-542
82. Pfeifer E, Pavela-Vrancic M, von Döhren H, Kleinkauf H (1995) Characterization of tyrocidine synthetase 1 (TY1): requirement of post-translational modification for peptide biosynthesis. Biochemistry 34: 7450-7459
83. Pieper R, Haese A, Schröder W, Zocher R (1995) Arrangement of catalytic sites in the multifunctional enzyme enniatin synthetase. Eur J Biochem 230: 119-126
84. Poland BW, Silva MM, Serra MA, Cho Y, Kim KH, Harris EMS, Honzatko RB (1993) Crystal structure of adenylosuccinate synthetase from Escherichia coli. Evidence for convergent evolution of GTP-binding domains. J Biol Chem 268: 25334-25342
85. Portillo F, Serrano R (1988) Dissection of functional domains of the yeast proton-pumping ATPase by site directed mutagenesis. EMBO J 7: 1793-1798
86. Raibaud A, Zalacain M, Holt TG, Tizard R, Thompson CJ (1991) Nucleotide sequence analysis reveals linked N-acetyl hydrolase, thioesterase, transport, and regulatory genes encoded by the bialaphos biosynthetic gene cluster of Streptomyces hygroscopicus. J Bacteriol 173: 4454-4462
87. Rossmann MG, Moras D, Olsen KW (1974) Chemical and biological evolution of a nucleotide-binding protein. Nature 250: 194-199
88. Rusnak F, Sakaitani M, Drueckhammer D, Reichert J, Walsh CT (1991) Biosynthesis of the Escherichia coli siderophore enterobactin: sequence of the entF gene, expression and purification of EntF, and analysis of covalent phosphopantetheine. Biochemistry 30: 2916-2927
89. Safford R, Windust JHC, Lucas C, De Silva J, James CM, Hellyer A, Smith CG, Slabas AR, Hughes SG (1988) Plastid-localised seed acyl-carrier protein of Brassica napus is encoded by a distinct, nuclear multigene family. Eur J Biochem 174: 287-295
90. Saito F, Hori K, Kanda M, Kurotsu T, Saito Y (1994) Entire nucleotide sequence for Bacillus brevis Nagano Grs2 gene encoding gramicidin S synthetase 2: a multifunctional peptide synthetase. J Biochem (Tokyo) 116: 357-367
91. Saito M, Hori K, Kurotsu T, Kanda M, Saito Y (1995) Three conserved glycine residues in valine activation of gramicidin S synthetase 2 from Bacillus brevis. J Biochem (Tokyo) 117: 276-282
92. Saraste M, Sibbald PR, Wittinghofer A (1990) The P-loop- a common motif in ATP- and GTP-binding proteins. TIBS 15: 430-434
93. Schimmel P (1987) Aminoacyl-tRNA synthetases: General scheme of structure-function relationships in the polypeptides and recognition of transfer RNAs. Annu Rev Biochem 56: 125-158
94. Schimmel P (1991) Classes of aminoacyl-tRNA synthetases and the establishment of the genetic code. Trends Biochem Sci 16: 1-3
95. Schimmel P, Schmidt E (1995) Making connections: RNA dependent amino acid recognition. Trends Biochem Sci 20: 1-2
96. Schlumbohm W, Stein T, Ullrich C, Vater J, Krause M, Marahiel MA, Kruft V, Wittmann-Liebold B (1991) An active site serine is involved in covalent substrate amino acid binding at each reaction center of gramicidin S synthetase. J Biol Chem 266: 23135-23141
97. Schofield PR, Watson JM (1986) DNA Sequence of Rhizobium trifolii nodulation genes reveales a reiterated and potentially regulatory sequence preceding nodABC and nodFE. Nucleic Acids Res 14: 2891-2903
98. Scott-Craig JS, Panaccione DG, Pocard J-A, Walton JD (1992) The cyclic peptide synthetase catalyzing HC-toxin production in the filamentous fungus Cochliobolus carbonum is encoded by a 15.7-kilobase open reading frame. J Biol Chem 267: 26044-26049
99. Shearman CA, Rossen L, Johnston AWB, Downie JA (1986) The Rhizobium leguminosarum nodulation gene nodF encodes a polypeptide similar to acyl carrier protein and is regulated by nodD plus a factor in pea root exudate. EMBO J 5: 647-652
100. Sherman DH, Malpratida F, Bibb J, Kieser HM, Bibb MJ, Hopwood DA (1989) Structure and deduced function of the granaticin producing polyketide synthase gene cluster of Streptomyces violaceoruber Tu22. EMBO J 8: 2717-2725
101. Shiau CY, Baldwin JE, Byford MF, Sobey WJ, Schofield CJ (1995) δ-L-(α-Aminoadipoyl)-L-cysteinyl-D-valine synthetase: the order of peptide bond formation and timing of the epimerisation reaction. FEBS Lett 358: 97-100
102. Skarpeid H-J, Zimmer T-L, Shen B, von Döhren H (1990a) The proline-activating activity of the multienzyme gramicidin S synthetase 2 can be recovered on a 115-kDa tryptic fragment. Eur J Biochem 187: 627-633
103. Skarpeid H-J, Zimmer T-L, von Döhren H (1990b) On the domain structure of the multienzyme gramicidin S synthetase 2. Isolation of domains activating valine and leucine. Eur J Biochem 189: 517-522
104. Smith DJ, Burnham MKR, Bull JH, Hodgson JE, Ward JM, Browne P, Brown J, Barton B, Earl AJ, Turner G (1990) β-lactam antibiotic biosynthetic genes have been conserved in clusters in prokaryotes and eukaryotes. EMBO J 9: 741-747
105. Srere PA (1987) Complexes of sequential metabolic enzymes. Annu Rev Biochem 56: 89-124
106. Staab JF, Elkins MF, Earhart CF (1989) Nucleotide sequence of the Escherichia coli entE gene. FEMS Microbiol Lett 59: 15-20
107. Stachelhaus T, Marahiel MA (1995a) Modular structure of genes encoding multifunctional peptide synthetases required for nonribosomal peptide biosynthesis. FEMS Microbiology Lett 125: 3-14
108. Stachelhaus T, Marahiel MA (1995b) Modular structure of peptide synthetases revealed by dissection of the multifunctional enzyme GrsA. J Biol Chem 270: 6163-6169
109. Stachelhaus T, Schneider A, Marahiel MA (1995) Rational design of peptide antibiotics by targeted replacement of bacterial and fungal domains. Science 269: 69-72
110. Stein T, Vater J, Kruft V, Wittmann-Liebold B, Franke P, Panico M, Dowell RM, Morris HR (1994) Detection of 4′-phosphopantetheine at the thioester binding site for L-valine of gramicidin S synthetase 2. FEBS Lett 340: 39-44
111. Stein T, Kluge B, Vater J, Franke P, Otto A, Wittmann-Liebold B (1995) Gramicidin S synthetase 1 (phenylalanine racemase), a prototype of amino acid racemases containing the cofactor 4′-phosphopantetheine. Biochemistry 34: 4633-4642
112. Taylor W, Green NM (1989) The predicted secondary structures of the nucleotide-binding sites of six cation-transporting ATPases lead to a probable tertiary fold. Eur J Biochem 179: 241-248
113. Tokita K, Hori K, Kurotsu T, Kanda M, Saito Y (1993) Effect of single base substitutions at glycine-870 codon of gramicidin S synthetase 2 gene on proline activation. J Biochem (Tokyo) 114: 522-527
114. Traut TW (1994) The functions and consensus motifs of nine types of peptide segments that form different types of nucleotide-binding sites. Eur J Biochem 222: 9-19
115. Turgay K, Krause M, Marahiel MA (1992) Four homologous domains in the primary structure of GrsB are related to domains in a superfamily of adenylate-forming enzymes. Mol Microbiol 6: 529-546
116. Ullrich C, Kluge B, Palacz Z, Vater J (1991) Cell-free biosynthesis of surfactin, a cyclic lipopeptide produced by Bacillus subtilis. Biochemistry 30: 6503-6508
117. Vanaman TC, Wakil SJ, Hill RL (1968) The complete amino acid sequence of the acyl carrier protein of Escherichia coli. J Biol Chem 243: 6420-6431
118. van Liempt H, Palissa H, Pfeifer E, Schwecke T, Weckermann R, von Döhren H, Kleinkauf H (1993) ACV-synthetase: implications of the amino-acid sequence data for the thiotemplate mechanism of peptide biosynthesis. In: Kleinkauf H, von Döhren H (eds) 50 years of penicillin application-history and trends. Publica, Prague, pp 136-144
119. Vater J (1990) Gramicidin S synthetase. In: Kleinkauf H, von Döhren H (eds) Biochemistry of peptide antibiotics, de Gruyter, Berlin, pp 33-55
120. Vollenbroich D, Kluge B, D'Souza C, Zuber P, Vater J (1993) Analysis of a mutant amino acid-activating domain of surfactin synthetase bearing a serine-to-alanine substitution at the site of carboxylthioester formation. FEBS Lett 325: 220-224
121. Vollenbroich D, Mehta N, Zuber P, Vater J, Kamp RM (1994) Analysis of surfactin synthetase subunits in srf A mutants of Bacillus subtilis OKB105. J Bacteriol 176: 395-400
122. Walker JE, Saraste M, Runswick MJ, Gay NJ (1982) Distantly related sequences in the α-and β-subunits of ATP-synthase, myosin, kinases and other ATP-requiring enzymes and a common nucleotide binding fold. EMBO J 1: 945-951
123. Walsh CT (1989) Enzymes in the D-alanine branch of bacterial cell wall peptidoglycan assembly. J Biol Chem 264: 2393-2396
124. Walton JD (1987) Two enzymes involved in biosynthesis of the host-selective phytotoxin HC-toxin. Proc Natl Acad Sci USA 84: 8444-8447
125. Weber G, Schörgendorfer K, Schneider-Scherzer E, Leitner E (1994) The peptide synthetase catalyzing cyclosporine production in Tolypocladium niveum is encoded by a giant 45.8 kilobase open reading frame. Current Genetics 26: 120-125
126. Weckermann R, Fürbaß R, Marahiel MA (1988) Complete nucleotide sequence of the tycA gene coding the tyrocidine synthetase 1 from Bacillus brevis. Nucleic Acids Res 16: 11841
127. Witkowski A, Naggert J, Mikkelsen J, Smith S (1987) Molecular cloning and sequencing of a cDNA encoding the acyl carrier protein and its flanking domains in the mammalian fatty acid synthetase. Eur J Biochem 165: 601-606
128. Wittinghofer A, Pai E (1991) The structure of Ras protein: a model for a universal switch. Trends Biochem Sci 16: 382-391
129. Wohlleben W, Alijah R, Dorendorf J, Hillemann D, Nussbaumer B, Pelzer S (1992) Identification and characterization of phosphinotricin-tripeptide biosynthetic genes in Streptomyces viridochromogenes. Gene 115: 127-132
130. Yoshida M, Amano T (1995) A common topology of proteins catalyzing ATP-triggered reactions. FEBS Lett 359: 1-5
131. Yuan Z, Liu W, Hammes GG (1988) Molecular cloning and sequencing of DNA complementary to chicken liver fatty acid synthase mRNA. Proc Natl Acad Sci USA 85: 6328-6331
132. Zuber P, Nakano MM, Marahiel MA (1993) Peptide antibiotics. In: Sonenshein AL, Hoch JA, Losick R (eds) Bacillus subtilis and other gram-positive bacteria. American Society for Microbiology, Washington, pp 897-916