Complex enzymes in microbial natural product biosynthesis. Part B, Polyketides, aminocoumarins and carbohydrates / edited by David A. Hopwood.

Format:

Book

Contributor:

Hopwood, D. A.

Series:

Methods in enzymology ; v. 459.

Methods in enzymology, 0076-6879 ; v. 459

Language:

English

Subjects (All):

Biosynthesis.

Polyketides--Synthesis.

Polyketides.

Peptides--Synthesis.

Peptides.

Carbohydrates--Synthesis.

Carbohydrates.

Physical Description:

xlvii, 581 pages, 16 unnumbered pages of plates : illustrations (some color) ; 24 cm.

Other Title:

Polyketides, aminocoumarins and carbohydrates

Place of Publication:

Amsterdam, Netherlands ; Boston, Mass. : Academic Press/Elsevier, [2009]

Contents:

Section I Polyketides 1

1 Introduction to Polyketide Biosynthesis / Kira J. Weissman 3

1 Introduction 3

Acknowledgment 13

References 13

2 Structural Enzymology of Polyketide Synthases / Shiou-Chuan (Sheryl) Tsai, Brian Douglas Ames 17

1 Introduction 18

2 Fatty Acid Synthase 19

3 Different Types of PKS and a Summary of Structural Work 21

4 Structural Enzymology of Individual Domains 22

5 Summary and Future Prospects 39

Acknowledgments 40

References 40

3 Fungal Type I Polyketide Synthases / Russell J. Cox, Thomas J. Simpson 49

1 Introduction 50

2 Partially Reducing PKSs: 6-MethylSalicylate Synthase 54

3 Nonreducing PKSs 57

4 Highly Reducing PKSs 66

5 NR/HR PKS Hybrid Systems: Zearalenone (ZAE1 and ZAE2) 72

6 Conclusions 74

References 74

4 Tandem Acyl Carrier Protein Domains in Polyunsaturated Fatty Acid Synthases / Hui Jiang, Scott R. Rajski, Ben Shen 79

1 Introduction 80

2 Methods 85

3 Conclusion 93

Acknowledgment 95

References 96

5 Iterative Type I Polyketide Synthases for Enediyne Core Biosynthesis / Geoffrey P. Horsman, Steven G. Van Lanen, Ben Shen 97

1 Introduction 98

2 Methods 100

3 Conclusion 109

Acknowledgment 111

References 111

6 The DEBS Paradigm for Type I Modular Polyketide Synthases and Beyond / Leonard Katz 113

1 Introduction 114

2 DEBS and the Concept of a Module 114

3 Beyond the DEBS Paradigm 119

4 Conclusion 136

References 136

7 Formation and Characterization of Acyl Carrier Protein-Linked Polyketide Synthase Extender Units / Yolande A. Chan, Michael G. Thomas 143

1 Introduction 144

2 Overproduction and Purification of Recombinant Proteins 147

3 Formation and Characterization of Hydroxymalonyl-ACP and Aminomalonyl-ACP 151

References 161

8 Type I Polyketide Synthases That Require Discrete Acyltransferases / Yi-Qiang Cheng, Jane M. Coughlin, Si-Kyu Lim, Ben Shen 165

1 Introduction 166

2 Methods 174

3 Conclusion 182

Acknowledgment 183

References 183

9 The Enzymology of Polyether Biosynthesis / Tiangang Liu, David E. Cane, Zixin Deng 187

1 Introduction 188

2 Genetic Mining and Functional Analysis of Genes Specific to Polyether Biosynthetic Pathways 191

3 Premonensin, the Parent Unsaturated Monensin Polyketide 195

4 Epoxidases MonCl, NigCl, and NanO 198

5 Epoxide Hydrolases MonBI/BII, NigBI/BII, NanI, and Lsd19 199

6 NanE, a Polyether-Specific Thioesterase 201

7 Assay of Polyether Thioesterase Activity 206

8 Transcriptional Analysis of the Nanchangmycin Biosynthetic Pathway Genes 209

9 Conclusions 210

Acknowledgments 210

References 211

10 Enzymology of the Polyenes Pimaricin and Candicidin Biosynthesis / Juan F. Martin, Jesus F. Aparicio 215

1 Introduction 216

2 Pimaricin as a Prototype of Small Polyenes: Discovery and Properties 217

3 Pimaricin Biosynthesis in S. natalensis 218

4 Regulation of Pimaricin Biosynthesis 224

5 Candicidin: A Prototype of "Aromatic" Polyenes 228

6 The Candicidin/FR-008 Gene Cluster 229

7 Biosynthesis of PABA: The pabAB and pabC Genes 230

8 The Polyketide Synthases 233

9 Monooxygenase Genes: Modifications of the Polyketide Chain 234

10 Transporter Genes 235

11 Genes Related to Mycosamine Biosynthesis 236

12 Regulatory Genes 236

13 Phosphate Represses Expression of the pabAB Gene 237

14 Future Perspectives 237

Acknowledgments 238

References 238

11 Genetic Analysis of Nystatin and Amphotericin Biosynthesis / Sergey Zotchev, Patrick Caffrey 243

1 Introduction 244

2 Gene Inactivation and Replacement in the Nystatin Producer Streptomyces noursei 246

3 Gene Inactivation and Replacement in the Amphotericin Producer Streptomyces nodosus 249

4 Production, Purification, and Characterization of Novel Amphotericin- and Nystatin-Related Polyenes 254

5 Conclusion 256

Acknowledgment 256

References 256

12 Polyketide Versatility in the Biosynthesis of Complex Mycobacterial Cell Wall Lipids / Tarun Chopra, Rajesh S. Gokhale 259

1 Introduction 260

2 Acetate and Propionate Feeding Studies 265

3 Genome Sequencing and Identification of Polyketide Synthases 266

4 Mycobacterial Polyketide Synthases 267

5 Techniques to Characterize PKS Enzymes 282

References 284

13 Genetic Engineering to Produce Polyketide Analogues / Christopher D. Reeves, Eduardo Rodriguez 295

1 Introduction 296

2 AT Domain Replacement to Alter a-Carbon Substitution 300

3 Procedure for Engineering AT Replacements in the Chromosome 301

4 Engineering b-Carbon Processing 305

5 Engineering when only a Single Crossover Event is Possible 308

6 Heterologous Expression of Engineered PKS Genes 309

7 Chemobiosynthesis 311

8 Mutasynthesis 313

9 Gene Knockouts to Obtain Analogues 314

References 315

14 Design and Synthesis of Pathway Genes for Polyketide Biosynthesis / Salvador Peiru, Hugo Gramajo, Hugo G. Menzella 319

1 Introduction 320

2 Redesign of PKS Genes to Accommodate Unique Restriction Sites Flanking Individual Components and for Efficient Expression in E. coli 322

3 Validation of Synthetic PKS Gene Design 324

4 A Rapid Assay to Identify Productive Combinations of PKS Modules 327

5 Assembly of Larger Polyketide Synthases Using Information Gained with the Bimodular Assay 330

6 Design and Construction of Synthetic Operons for the Expression of Sugar Pathway Genes 332

References 335

15 Heterologous Production of Polyketides in Bacteria / Eduardo Rodriguez, Hugo G. Menzella, Hugo Gramajo 339

1 Introduction 340

2 General Considerations for the Heterologous Expression of Polyketide Pathways 341

3 S. coelicolor as a Model System for Heterologous Expression of Polyketides 344

4 Procedure for the Heterologous Production of Polyketides in S. coelicolor 347

5 System Improvements for the Heterologous Production of Polyketides in Streptomyces spp 349

6 Recent Developments for the Production of Polyketides in Nonactinomycete Bacteria 357

References 360

16 In Vitro Analysis of Type II Polyketide Synthase / Wenjun Zhang, Yi Tang 367

1 Introduction 368

2 Expression and Purification of Type II PKSs 371

3 In Vitro Activity Assays 376

Acknowledgments 389

References 390

17 Bacterial Fatty Acid Synthesis and its Relationships with Polyketide Synthetic Pathways / John E. Cronan, Jacob Thomas 395

1 Introduction 396

2 Bacterial Fatty Acids 396

3 Acyl Carrier Protein, the Key Component of Bacterial Fatty Acid Synthesis 397

4 Overview of the Reactions of Fatty Acid Biosynthesis 400

5 The Initiation Steps of Fatty Acid Synthesis 402

6 The Enzymes of the Fatty Acid Elongation Cycle 404

7 Unsaturated Fatty Acid Synthesis in E. coli 407

8 The Abundant Exceptions to the E.

coli Fatty Acid Synthesis Paradigm 410

9 Relationships between Fatty Acid Synthesis and Polyketide Synthesis 412

10 Methods for Study of Bacterial Fatty Acid Synthesis 415

References 426

Section II Aminocoumarins 435

18 Aminocoumarins: Mutasynthesis, Chemoenzymatic Synthesis, and Metabolic Engineering / Lutz Heide 437

1 Introduction 438

2 Generation of Integrative Cosmids and Heterologous Expression of Novobiocin, Clorobiocin, and Coumermycin A₁ Gene Clusters 441

3 Generation of Single and or Multiple Deletions in the Integrative Cosmids 442

4 Mutasynthetic Generation of New Aminocoumarin Antibiotics 444

5 In Vitro Amide Synthetase Assays for the Identification of Suitable Ring A Analogues for Mutasynthesis 446

6 Use of Various Amide Synthetase Genes for Expanding Mutasynthesis Product Range 447

7 Generation of Substrates for Chemoenzymatic Synthesis 447

8 Chemoenzymatic Synthesis of New Clorobiocin Analogues 449

9 Generation of New Aminocoumarin Antibiotics by Metabolic Engineering 451

10 Conclusion 453

Acknowledgments 453

References 454

Section III Carbohydrates 457

19 Enzymology of Aminoglycoside Biosynthesis-Deduction from Gene Clusters / Udo F. Wehmeier, Wolfgang Piepersberg 459

1 Introduction 460

2 Some Key Enzymes in the Biosyntheses of Aminoglycoside Antibiotics 469

3 Acarbose and Related Metabolites 478

References 487

20 Biosynthetic Enzymes for the Aminoglycosides Butirosin and Neomycin / Fumitaka Kudo, Tadashi Eguchi 493

1 Introduction 494

2 General Method to Investigate Functions of the Biosynthetic Enzymes for Aminoglycosides 499

3 Neamine Biosynthetic Enzymes (Enzymes 1.

Notes:

Includes bibliographical references and index.

ISBN:

9780123745910

0123745918

OCLC:

319600649