It is quite amazing that the oldest group of medically useful antibiotics, the p-Iactams, are still providing basic microbiologists, biochemists, and clinicians with surprises over 50 years after Fleming's discovery of penicillin production by Penicillium. By the end of the 1950s, the future of the penicillins seemed doubtful as resistant strains of Staphylococcus aureus began to increase in hospital populations. However, the development of semisynthetic penicillins provided new structures with resistance to penicillinase and with broad-spectrum activity. In the 1960s, the discovery of…mehr
It is quite amazing that the oldest group of medically useful antibiotics, the p-Iactams, are still providing basic microbiologists, biochemists, and clinicians with surprises over 50 years after Fleming's discovery of penicillin production by Penicillium. By the end of the 1950s, the future of the penicillins seemed doubtful as resistant strains of Staphylococcus aureus began to increase in hospital populations. However, the development of semisynthetic penicillins provided new structures with resistance to penicillinase and with broad-spectrum activity. In the 1960s, the discovery of cephalosporin C production by Cephalosporium and its conversion to valuable broad-spectrum antibiotics by semisynthetic means excited the world of chemotherapy. In the early 1970s, the 40-year-old notion that p-lactams were produced only by fungi was destroyed by the discovery of cephamycin production by Streptomyces. Again this basic discovery was exploited by the development of the semisynthetic cefoxitin, which has even broader activity than earlier p-lactams. Later in the 1970 s came the discoveries of nocardicins from Nocardia, clavulanic acid from Streptomyces, and the carbapenems from Streptomyces. Now in the 1980s we learn that p-lactams are produced even by unicellular bacteria and that semisynthetic derivatives of these monobactams may find their way into medicine. Indeed, the future of the prolific p-lactam family seems brighter with each passing decade.Hinweis: Dieser Artikel kann nur an eine deutsche Lieferadresse ausgeliefert werden.
1 History of ?-Lactam Antibiotics.- A. The Past Fifty Years.- B. The Future.- References.- 2 Mode of Action of ?-Lactam Antibiotics - A Microbiologist's View.- A. Introduction.- B. Journey of the Extracellular Antibiotic to the Intracellular Targets.- C. The Biochemical Targets of ?-Lactam Antibiotics.- D. Physiological Consequences of ?-Lactam Inhibition.- E. Variations in the Physiological Effects of Penicillins.- F. Environmental Factors That Modulate the Antibacterial Effects of Penicillin.- G. Conclusion.- References.- 3 Strain Improvement and Preservation of ?-Lactam-Producing Microorganisms.- A. Introduction.- B. Distribution of ?-Lactam Antibiotics and Related Metabolites in Nature.- C. Strain Improvement Programs in Commercially Important ?-Lactam Fermentation Organisms.- D. Actinomycetes Producing New ?-Lactam Antibiotics.- E. Unicellular Bacteria Producing Sulfazecins and Related Structures.- F. Maintenance and Long-Term Preservation of Strains of Penicillium chrysogenum and Acremonium chrysogenum.- References.- 4 Genetics of ?-Lactam-Producing Fungi.- A. Introduction.- B. Aspergillus nidulans.- C. Penicillium chrysogenum.- D. Cephalosporium acremonium.- E. Recombination Between Naturally Incompatible Fungi.- References.- 5 Genetics of ?-Lactam-Producing Actinomycetes.- A. Introduction.- B. ?-Lactam Antibiotics and the Actinomycetales.- C. Streptomyces Genetics.- D. Antibiotic Production in Actinomycetes.- E. The Genetics of ?-Lactam Antibiotics and the Future.- References.- 6 Biosynthesis of ?-Lactam Antibiotics.- A. Introduction.- B. Hydrophobic ?-Lactam Antibiotics.- C. Hydrophilic ?-Lactam Antibiotics.- D. Antibiotic Production by Pairs of Blocked Mutants.- E. Novel ?-Lactam Antibiotics.- References.- 7 Regulation of Biosynthesis of?-Lactam Antibiotics.- A. Introduction.- B. Carbon Catabolite Regulation.- C. Nitrogen Metabolite Regulation.- D. Regulation at the Level of Sulfur Metabolism.- E. Lysine Metabolism and Antibiotic Biosynthesis.- F. Control of ?-Lactam Specific Enzymes at the Level of Secondary Metabolism.- G. End-Product Regulation.- H. Summary and Future Outlook.- References.- 8 Biochemical Engineering and ?-Lactam Antibiotic Production.- A. Introduction.- B. Penicillin Fermentation - Current Status.- C. Growth Monitoring and Control - Method of Approach.- D. Effect of Growth on Penicillin Production.- E. Effect of the Use of Corn-Steep Liquor.- F. Maintenance Demand as a Fermentation Variable.- G. Overall Conversion Yield of Glucose to Penicillin- Ppis.- H. Summary.- References.- 9 Screening for New ?-Lactam Antibiotics.- A. Introduction.- B. Rationale for Screening of ?-Lactam Antibiotics.- C. Finding ?-Lactam-Producing Microorganisms.- D. Screening Systems Which Detect ?-Lactams.- E. Future Trends.- F. A Hypothetical Screening Model.- References.- 10 High-Performance Liquid Chromatography of ?-Lactam Antibiotics.- A. Introduction.- B. Penicillin Antibiotics.- C. Cephalosporin Antibiotics.- D. Other ?-Lactam Compounds.- E. Oxy-?-L actams.- F. Concluding Remarks.- References.- 11 Strategy in the Total Synthesis of ?-Lactam Antibiotics.- A. Introduction.- B. ?-Lactam Closure.- C. 2+2 Annelations.- D. Monocyclic ?-Lactam Antibiotics.- E. Examples Involving Prior Construction of the Azetidinone.- F. Penicillin Total Synthesis - Sheehan.- G. Cefoxitin Total Synthesis - Merck.- H. Nocardicin Total Synthesis - Wasserman.- I. Total Synthesis of (±)-Clavulanic Acid - Beecham.- J. Cephalosporin C Total Synthesis - Woodward.- K. Penicillin Total Synthesis -Baldwin.- L. Synthesis of the Penem Nucleus - Woodward.- M. Total Synthesis of (+)-Thienamycin - Merck.- N. Conclusion.- References.
1 History of ?-Lactam Antibiotics.- A. The Past Fifty Years.- B. The Future.- References.- 2 Mode of Action of ?-Lactam Antibiotics - A Microbiologist's View.- A. Introduction.- B. Journey of the Extracellular Antibiotic to the Intracellular Targets.- C. The Biochemical Targets of ?-Lactam Antibiotics.- D. Physiological Consequences of ?-Lactam Inhibition.- E. Variations in the Physiological Effects of Penicillins.- F. Environmental Factors That Modulate the Antibacterial Effects of Penicillin.- G. Conclusion.- References.- 3 Strain Improvement and Preservation of ?-Lactam-Producing Microorganisms.- A. Introduction.- B. Distribution of ?-Lactam Antibiotics and Related Metabolites in Nature.- C. Strain Improvement Programs in Commercially Important ?-Lactam Fermentation Organisms.- D. Actinomycetes Producing New ?-Lactam Antibiotics.- E. Unicellular Bacteria Producing Sulfazecins and Related Structures.- F. Maintenance and Long-Term Preservation of Strains of Penicillium chrysogenum and Acremonium chrysogenum.- References.- 4 Genetics of ?-Lactam-Producing Fungi.- A. Introduction.- B. Aspergillus nidulans.- C. Penicillium chrysogenum.- D. Cephalosporium acremonium.- E. Recombination Between Naturally Incompatible Fungi.- References.- 5 Genetics of ?-Lactam-Producing Actinomycetes.- A. Introduction.- B. ?-Lactam Antibiotics and the Actinomycetales.- C. Streptomyces Genetics.- D. Antibiotic Production in Actinomycetes.- E. The Genetics of ?-Lactam Antibiotics and the Future.- References.- 6 Biosynthesis of ?-Lactam Antibiotics.- A. Introduction.- B. Hydrophobic ?-Lactam Antibiotics.- C. Hydrophilic ?-Lactam Antibiotics.- D. Antibiotic Production by Pairs of Blocked Mutants.- E. Novel ?-Lactam Antibiotics.- References.- 7 Regulation of Biosynthesis of?-Lactam Antibiotics.- A. Introduction.- B. Carbon Catabolite Regulation.- C. Nitrogen Metabolite Regulation.- D. Regulation at the Level of Sulfur Metabolism.- E. Lysine Metabolism and Antibiotic Biosynthesis.- F. Control of ?-Lactam Specific Enzymes at the Level of Secondary Metabolism.- G. End-Product Regulation.- H. Summary and Future Outlook.- References.- 8 Biochemical Engineering and ?-Lactam Antibiotic Production.- A. Introduction.- B. Penicillin Fermentation - Current Status.- C. Growth Monitoring and Control - Method of Approach.- D. Effect of Growth on Penicillin Production.- E. Effect of the Use of Corn-Steep Liquor.- F. Maintenance Demand as a Fermentation Variable.- G. Overall Conversion Yield of Glucose to Penicillin- Ppis.- H. Summary.- References.- 9 Screening for New ?-Lactam Antibiotics.- A. Introduction.- B. Rationale for Screening of ?-Lactam Antibiotics.- C. Finding ?-Lactam-Producing Microorganisms.- D. Screening Systems Which Detect ?-Lactams.- E. Future Trends.- F. A Hypothetical Screening Model.- References.- 10 High-Performance Liquid Chromatography of ?-Lactam Antibiotics.- A. Introduction.- B. Penicillin Antibiotics.- C. Cephalosporin Antibiotics.- D. Other ?-Lactam Compounds.- E. Oxy-?-L actams.- F. Concluding Remarks.- References.- 11 Strategy in the Total Synthesis of ?-Lactam Antibiotics.- A. Introduction.- B. ?-Lactam Closure.- C. 2+2 Annelations.- D. Monocyclic ?-Lactam Antibiotics.- E. Examples Involving Prior Construction of the Azetidinone.- F. Penicillin Total Synthesis - Sheehan.- G. Cefoxitin Total Synthesis - Merck.- H. Nocardicin Total Synthesis - Wasserman.- I. Total Synthesis of (±)-Clavulanic Acid - Beecham.- J. Cephalosporin C Total Synthesis - Woodward.- K. Penicillin Total Synthesis -Baldwin.- L. Synthesis of the Penem Nucleus - Woodward.- M. Total Synthesis of (+)-Thienamycin - Merck.- N. Conclusion.- References.
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