天然产物 2.0 版：将基因与分子联系起来。
Natural products version 2.0: connecting genes to molecules.
机构信息
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, USA.
出版信息
J Am Chem Soc. 2010 Mar 3;132(8):2469-93. doi: 10.1021/ja909118a.
Abstract
Natural products have played a prominent role in the history of organic chemistry, and they continue to be important as drugs, biological probes, and targets of study for synthetic and analytical chemists. In this Perspective, we explore how connecting Nature's small molecules to the genes that encode them has sparked a renaissance in natural product research, focusing primarily on the biosynthesis of polyketides and non-ribosomal peptides. We survey monomer biogenesis, coupling chemistries from templated and non-templated pathways, and the broad set of tailoring reactions and hybrid pathways that give rise to the diverse scaffolds and functionalization patterns of natural products. We conclude by considering two questions: What would it take to find all natural product scaffolds? What kind of scientists will be studying natural products in the future?
摘要
天然产物在有机化学的历史中扮演了重要的角色，它们作为药物、生物探针以及合成和分析化学家研究的目标仍然具有重要意义。在本篇观点文章中，我们探讨了将自然界小分子与编码它们的基因联系起来如何激发了天然产物研究的复兴，主要集中在聚酮和非核糖体肽的生物合成上。我们调查了单体生物发生、模板和非模板途径的连接化学，以及广泛的修饰反应和混合途径，这些途径产生了天然产物的多样化支架和功能化模式。最后，我们考虑了两个问题：找到所有天然产物支架需要什么？未来什么样的科学家将研究天然产物？
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2
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Biochemistry. 2009 Nov 3;48(43):10467-72. doi: 10.1021/bi9013165.
3
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