The Biology of B-Lactam Antibiotics

Contributors

Preface

Contents of Other Volumes

I. The Biosynthesis of β-Lactam Antibiotics

I. Introduction

II. Steps Common to Biosynthesis of Penicillins, Cephalosporins, and 7α-Methoxycephalosporins

III. The Enzymatic Conversion of IsopeniciUin N to Penicillium-Type Penicillins

IV. Mechanism of Penicillin G Excretion

V. Biosynthesis of Cephalosporins and 7α-Methoxycephalosporins

VI. Synthesis of Cephalosporins and 7α-Methoxycephalosporins

VII. Genes Associated with Conversion of Primary Metabolites to Penam and Ceph-3-em Antibiotics

VIII. Distribution of Cephalosporins, 7α-Methoxycephalosporins, and Penicillium-Type Penicillins

IX. New Classes of β-Lactam Antibiotics and Their Biosyntheses

X. The Relationship of β-Lactam Bond Formation in Penam, Clavam, 1-Carbapen-2-em, and Nocardicin Antibiotics

XI. The Future: Significant Questions and New Possibilities

References


2. β-Lactam-Producing Microorganisms: Their Biology and Fermentation Behavior

I. Introduction

II. Genetic Aspects of β-Lactam Synthesis in Strains of Penicillium chrysogenum and Acremonium chrysogenum

III. Maintenance and Productivity of High-Yielding Strains of P. chrysogenum and A. chrysogenum

IV. Process Control in the Penicillin and CephalosporinC Fermentations

V. New β-Lactam Antibiotics from Streptomyces and Nocardia

VI. Cell-Free Biosynthetic Studies with Protoplasts of P. chrysogenum and A. chrysogenum

VII. Biochemical Control Mechanisms Affecting β-Lactam Synthesis

VIII. Applications of the Techniques of Protoplast Fusion and Recombinant DNA to β-Lactam Antibiotics

References


3. Physiology, Biochemistry, and Inactivation of β-Lactamases

I. Introduction

II. Methodology

III. The Enzymes

IV. β-Lactamase Inactivators

References


4. β-Lactam Antibiotics: Biochemical Modes of Action

I. Background

II. Bacterial Cell Walls

III. Substrate Analog Hypothesis

IV. Penicillin-Binding Proteins (PBPs)

V. Interactions of PBPs with β-Lactams

VI. Structural Studies of PBPs

VII. Functions of PBPs in Vivo

VIII. β-Lactams as Substrate Analogs

IX. Autolysins and the Mechanism of Bacterial Lysis

X. β-Lactam Permeability Problems

XI. Conclusions

References


5. β-Lactam Antibiotics in Clinical Medicine

I. Prolog

II. The Advent of Penicillin

III. Semisynthetic Penicillin Derivatives of the 1960s and 1970s

IV. Cephalosporins: A New Class of β-Lactams

V. New Cephalosporins

VI. Third-Generation Parenteral Penicillins

VII. Expanded-Spectrum Cephalosporins

VIII. Unique New β-Lactams

IX. Guidance from the Past: Perspectives for the 1980s

References


6. The Relationship between Inhibition of Cell Wall Synthesis and Bacterial Lethality

I. Introduction

II. The Secondary Consequences of Inhibition of Cell Wall Assembly

III. Events that Accompany β-Lactam Inhibition of Peptidoglycan Aβembly in Highly Tolerant Bacteria

IV. Regulation of Endogenous Peptidoglycan Hydrolases

V. Other Reported Secondary Consequences of Inhibition of Peptidoglycan Assembly

VI. Cell Surface Growth and Division

VII. Concluding Remarks

References


7. Monobactams

I. Introduction

II. Isolation and Structure Determination

III. Synthesis of Monobactams

IV. Microbiological Activity of Monobactams

V. Conclusion

References

Appendices

Appendix A: β-Lactam Antibiotics in Commercial Use or Clinical Investigation

Appendix B: Introduction of a 7-Methoxyl Group into Penicillins or Cephalosporins

Appendix C: Total Synthesis of Substituted Azetidinone 2-Carboxylates and Their Utilization

Appendix D: Cell-Free Biosynthesis of Cephalosporins from Penicillin

Appendix E: Assays for Penicillin-Binding Proteins (PBPs)

Index