Natural products with anti-infective activity are largely of polyketide or peptide origin. The nascent scaffolds typically undergo further enzymatic morphing to produce mature active structures. Two kinds of common constraints during maturation of immature scaffolds to active end point metabolites are macrocyclizations and hetrocyclizations. Each builds compact architectures characteristic of many high affinity, specific ligands for therapeutic targets. The chemical logic and enzymatic machinery for macrolactone and macrolactam formations are analyzed for antibiotics such as erythromycins, daptomycin, polymyxins, and vancomycin. In parallel, biosynthetic enzymes build small ring heterocycles, including epoxides, β-lactams, and β-lactones, cyclic ethers such as tetrahydrofurans and tetrahydropyrans, thiazoles, and oxazoles, as well as some seven- and eight-member heterocyclic rings. Combinations of fused heterocyclic scaffolds and heterocycles embedded in macrocycles reveal nature’s chemical logic for building active molecular frameworks in short efficient pathways.

中文翻译：

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大自然将大环化合物和杂环化合物构建到其抗菌框架中：破解生物合成策略

具有抗感染活性的天然产物主要来自聚酮或肽。新生支架通常经历进一步的酶促变形以产生成熟的活性结构。在未成熟支架成熟为活性终点代谢物的过程中，两种常见的限制条件是大环化和杂环化。每种都构建了紧凑的结构，这些结构具有许多高亲和力，特异性的治疗靶标配体。分析了大内酯和大内酰胺形成的化学逻辑和酶促机制，以分析抗生素，如红霉素，达托霉素，多粘菌素和万古霉素。同时，生物合成酶会形成小的环杂环，包括环氧化物，β-内酰胺和β-内酯，环醚（例如四氢呋喃和四氢吡喃），噻唑和恶唑，以及一些七元和八元杂环。融合在大环中的杂环支架和杂环的组合揭示了自然界的化学逻辑，可在较短的有效途径中构建活性分子框架。