Singh M P, Greenstein M
Natural Products Microbiology, Infectious Diseases Section, Wyeth-Ayerst Research, Pearl River, NY 10965, USA.
Curr Opin Drug Discov Devel. 2000 Mar;3(2):167-76.
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.
青霉素的意外发现以及磺胺的出现标志着抗生素时代的开端。尽管合成化合物在对抗细菌感染方面继续发挥着重要作用，但微生物天然产物的贡献不可低估。当今临床使用的绝大多数抗菌剂要么是微生物天然产物，要么是它们的类似物之一。寻找具有新作用模式的新型化学实体并优化其活性 微生物天然产物已被证明是具有多种生物活性的新型化合物的丰富来源。抗生素时代“黄金”时期的惊人成功产生了几种能够满足那个时期需求的药物，随后，经历了一段对寻找新抗生素投入减少的时期。然而，对微生物天然产物用于其他治疗应用的兴趣持续存在，并已证明是有成效的。最近抗生素耐药菌的出现增加，迫使许多人将注意力转向寻找新型抗生素，不出所料，微生物天然产物正被作为一个来源而受到认真探索。新的抗生素正在被分离出来，未充分利用的旧抗生素库也正在被重新审视。通过基因组学发现了新的细菌靶点，并且正在对微生物进行基因工程改造以产生新型代谢产物。
