Natural products and their derivatives are mainstays of our antibiotic drugs, but they are increasingly in peril. The combination of widespread multidrug resistance in once susceptible bacterial pathogens, disenchantment with natural products as sources of new drugs, lack of success using synthetic compounds and target-based discovery methods, along with shifting economic and regulatory issues, conspire to move investment in research and development away from the antibiotics arena. The result is a growing crisis in antibiotic drug discovery that threatens modern medicine. 21^st century natural product research is perfectly positioned to fill the antibiotic discovery gap and bring new drug candidates to the clinic. Innovations in genomics and techniques to explore new sources of antimicrobial chemical matter are revealing new chemistry. Increasing appreciation of the value of narrow-spectrum drugs and re-examination of once discarded chemical scaffolds coupled with synthetic biology methods to generate new compounds and improve yields offer new strategies to revitalize once moribund natural product programs. The increasing awareness that the combination of antibiotics with adjuvants, non-antibiotic compounds that overcome resistance and enhance drug activity, can rescue older chemical scaffolds, and concepts such as blocking pathogen virulence present orthogonal strategies to traditional antibiotics. In all these areas, natural products offer chemical matter, shaped by natural selection, that is privileged in this therapeutic area. Natural product research is poised to regain prominence in delivering new drugs to solve the antibiotic crisis.

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机遇天然产物在21^日世纪抗生素的发现

天然产物及其衍生物是我们抗生素药物的主要支柱，但它们正日益处于危险之中。曾经易感的细菌病原体广泛的多药耐药性，天然产物作为新药的来源逐渐消失，使用合成化合物和基于靶标的发现方法缺乏成功以及不断变化的经济和监管问题，这些共同作用共同推动了对研究和开发的投资。远离抗生素领域的发展。结果是抗生素药物发现的危机日益严重，威胁到现代医学。21^日世纪天然产品研究完全可以填补抗生素发现空白，并为临床带来新的候选药物。探索抗生素化学物质新来源的基因组学和技术创新正在揭示新的化学方法。窄谱药物价值的不断提高以及对曾经废弃的化学支架的重新检验，再加上合成新的化合物并提高产量的合成生物学方法，为一旦濒临灭绝的天然产物计划提供了新的战略。人们日益认识到，将抗生素与佐剂，能克服耐药性并增强药物活性的非抗生素化合物结合使用，可以挽救较旧的化学支架，而诸如阻断病原体毒力等概念提出了与传统抗生素正交的策略。在所有这些方面，天然产品可提供通过自然选择而形成的化学物质，这在该治疗领域具有优势。天然产物的研究准备重新获得在交付新药以解决抗生素危机方面的突出地位。