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Structure-based combinatorial protein engineering

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124:: some mutational pathways show steady, additive changes, whereas others show drastic jumps between contrasting product specificities with single mutational steps. Further, a metric was devised to describe the chemical distance of mutational steps to derive a chemical-based 128:
relating sequence variation to chemical output. These examples establish SCOPE as a standardized method for the construction of synthetic gene libraries from close or distantly related parental sequences to identify functional novelty among the encoded proteins.
43:, and evolution, although the technique is generally applicable for the creation of engineered proteins with commercially desirable properties. Combinatorial travel through sequence 35:) of defined composition designed from structural and probabilistic constraints of the encoded proteins. The development of this technique was driven by fundamental questions about 109:
lineage, which was biochemically characterized to recapitulate the evolutionary divergence of two modern day enzymes. The rapid evolvability of chemical diversity in
59:-independent recombination technique to enable the creation of multiple crossover libraries from distantly related genes. In this application, an “exon 240:
O'Maille PE, Tsai MD, Greenhagen BT, Chappell J, Noel JP (2004). "Gene library synthesis by structure-based combinatorial protein engineering".
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O'Maille PE, Malone A, Dellas N, Andes Hess B, Smentek L, Sheehan I, Greenhagen BT, Chappell J, Manning G, Noel JP (Oct 2008).
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O'Maille PE, Bakhtina M, Tsai MD (Aug 2002). "Structure-based combinatorial protein engineering (SCOPE)".
163: 277:"Quantitative exploration of the catalytic landscape separating divergent plant sesquiterpene synthases" 148: 71:) to explore global protein space. To create the corresponding library of genes, the breeding scheme of 173: 121: 32: 193: 138: 64: 56: 306: 263: 253: 228: 198: 36: 24: 296: 288: 245: 220: 92: 88: 178: 95: 83:
inbreeding to create all possible combinations of coding segments with variable linkages.
68: 60: 301: 276: 168: 153: 249: 224: 333: 125: 72: 324: 28: 183: 143: 117: 63:” design strategy was devised to assemble “equivalent” elements of structure ( 99: 80: 44: 310: 267: 232: 292: 188: 113: 110: 40: 158: 106: 91:
was used as the selection system to successfully identify functional
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were demonstrated through processes akin to both Darwinian
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strategy to selectively cross hybrid genes, a process of
244:. Methods in Enzymology. Vol. 388. pp. 75–91. 67:) with variability in the junctions linking them ( 17:Structure-based combinatorial protein engineering 105:SCOPE was then used to construct a synthetic 8: 55:At its inception, SCOPE was developed as a 300: 98:of minimal architecture with enhanced 7: 14: 1: 250:10.1016/S0076-6879(04)88008-X 225:10.1016/S0022-2836(02)00675-7 213:Journal of Molecular Biology 371: 87:in temperature-sensitive 340:Combinatorial chemistry 281:Nature Chemical Biology 85:Genetic complementation 27:technique for creating 164:Nucleic acid analogues 47:is the goal of SCOPE. 149:Expanded genetic code 345:Evolutionary biology 293:10.1038/nchembio.113 350:Protein engineering 242:Protein Engineering 174:Protein engineering 75:was adapted into a 194:Structural biology 139:Directed evolution 65:continental plates 355:Synthetic biology 199:Synthetic biology 37:protein structure 25:synthetic biology 362: 314: 304: 271: 236: 370: 369: 365: 364: 363: 361: 360: 359: 330: 329: 321: 274: 260: 239: 210: 207: 205:Further reading 179:Protein folding 135: 96:DNA polymerases 61:plate tectonics 53: 12: 11: 5: 368: 366: 358: 357: 352: 347: 342: 332: 331: 328: 327: 320: 319:External links 317: 316: 315: 287:(10): 617–23. 272: 258: 237: 206: 203: 202: 201: 196: 191: 186: 181: 176: 171: 169:Protein design 166: 161: 156: 154:Gene synthesis 151: 146: 141: 134: 131: 52: 49: 29:gene libraries 13: 10: 9: 6: 4: 3: 2: 367: 356: 353: 351: 348: 346: 343: 341: 338: 337: 335: 326: 323: 322: 318: 312: 308: 303: 298: 294: 290: 286: 282: 278: 273: 269: 265: 261: 259:9780121827939 255: 251: 247: 243: 238: 234: 230: 226: 222: 219:(4): 677–91. 218: 214: 209: 208: 204: 200: 197: 195: 192: 190: 187: 185: 182: 180: 177: 175: 172: 170: 167: 165: 162: 160: 157: 155: 152: 150: 147: 145: 142: 140: 137: 136: 132: 130: 127: 123: 119: 115: 112: 108: 103: 101: 97: 94: 90: 86: 82: 78: 74: 73:Gregor Mendel 70: 66: 62: 58: 50: 48: 46: 42: 38: 34: 30: 26: 22: 18: 325:SCOPE Patent 284: 280: 241: 216: 212: 104: 54: 20: 16: 15: 69:fault lines 51:Description 334:Categories 184:Proteomics 144:Enzymology 118:gradualism 100:phenotypes 126:phylogeny 122:saltation 114:synthases 81:iterative 45:spacetime 311:18776889 268:15289063 233:12206782 189:Proteome 133:See also 57:homology 41:function 33:lineages 302:2664519 111:terpene 89:E. coli 23:) is a 309:  299:  266:  256:  231:  159:Genome 107:enzyme 93:hybrid 21:SCOPE 307:PMID 264:PMID 254:ISBN 229:PMID 120:and 297:PMC 289:doi 246:doi 221:doi 217:321 77:PCR 336:: 305:. 295:. 283:. 279:. 262:. 252:. 227:. 215:. 102:. 39:, 313:. 291:: 285:4 270:. 248:: 235:. 223:: 31:( 19:(

Index

synthetic biology
gene libraries
lineages
protein structure
function
spacetime
homology
plate tectonics
continental plates
fault lines
Gregor Mendel
PCR
iterative
Genetic complementation
E. coli
hybrid
DNA polymerases
phenotypes
enzyme
terpene
synthases
gradualism
saltation
phylogeny
Directed evolution
Enzymology
Expanded genetic code
Gene synthesis
Genome
Nucleic acid analogues

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