Antibacterial leads from microbial natural products discovery.
The accidental discovery of penicillin and the advent of sulfanilamide marked the beginning of the antibiotic era. Although synthetic compounds have continued to play important roles in the fight against bacterial infections, the contribution of microbial natural products cannot be underestimated. A vast majority of the antibacterial agents in clinical use today are either microbial natural products or one of their analogs. Finding novel chemical entities with new modes of action and optimizing their activities Microbial natural products have been a proven, rich source of novel compounds with diverse biological activities. The astounding success of the 'golden' period of the antibiotic era delivered several capable of meeting the needs of that period, and subsequently, a period of diminished commitment to finding new antibiotics was experienced. An interest in microbial natural products for other therapeutic applications continued however, and has proved rewarding. The recent increase in the emergence of antibiotic-resistant bacteria has forced many to shift their attention towards finding novel antibiotics and not surprisingly, microbial natural products are being seriously pursued as a source. New antibiotics are being isolated and the old libraries of under-exploited antibiotics are being re-examined. Novel bacterial targets are being exposed through genomics and microorganisms are being genetically engineered for novel metabolites.
Singh
M P
MP
Natural Products Microbiology, Infectious Diseases Section, Wyeth-Ayerst Research, Pearl River, NY 10965, USA. singhm@war.wyeth.com
Greenstein
M
M