Chapter 30. Strategies in the Discovery of Drugs from Natural Sources

The history of cyclosporin A (Sandimmune®) revisited: Another point of view

“…We made no attempt to use the interesting strategy recommended by De Souza et al 58, namely that of experimental genetic recombination by fusion of microbial protoplasts in order to produce tailor-made metabolites -despite the fact that I was aware of such possibilities, having been the first to observe fusion of bacterial protoplasts 59. Drug research is an area particularly abundant in examples both of different kinds of inventions and discoveries, and of various ways in which progress has been achieved.…”

Discovery and development of new antimicrobial agents

“…The discovery and isolation of the lead structures for each of these classes have provided a unique starting point for chemical modification in attempts to improve their spectrum, pharmacokinetics, and human safety. Three basic approaches have been used to find new antibiotics from natural sources: (i) direct isolation from soil and marine microorganisms, (ii) genetic modification of known antibiotic-producing organisms to induce their production of novel metabolites, and (iii) diversion of natural metabolic pathways of antibiotic-producing organisms by introduction of substrate precursors into the fermentation system (150).…”

“…Reports of new antimi- (120). The majority of these new antibiotics isolated from fermentations have come from soil organisms of the genus Streptomyces, although in more recent efforts novel monobactams have been found in fermentations of Agrobacterium and Pseudomonas species (15,150,173). Continued refinement of the process of antibiotic discovery from natural products has substituted biochemical-based assays for those that rely on killing of the bacterial target organism (120).…”

Discovery and development of new antimicrobial agents.

“…One early study, for instance, estimated that, of 21,830 fermentation cultures tested, 6,464 produced antibiotics, 490 of which possessed activities of interest; 6 were eventually submitted for structural determinations, from which two novel structures were isolated (178) (120). The majority of these new antibiotics isolated from fermentations have come from soil organisms of the genus Streptomyces, although in more recent efforts novel monobactams have been found in fermentations of Agrobacterium and Pseudomonas species (15,150,173). Continued refinement of the process of antibiotic discovery from natural products has substituted biochemical-based assays for those that rely on killing of the bacterial target organism (120).…”