中文摘要：

很多微生物能够利用非核糖体肽合酶合成结构复杂、种类繁多、生物活性多样的小分子肽类化合物。组合生物合成是对控制抗生素生物合成的基因簇进行阻断、置换、重组或异源表达等遗传操作，从而达到利用生物技术和环境友好的手段构建化合物衍生物库的目的。组合生物合成在增加天然活性化合物的数量，改良天然化合物的生物学活性，提高天然化合物的产量，开发创新药物和酶制剂等领域都具有重要应用价值。近年来，非核糖体肽的组合生物合成研究取得了重要进展。本文就非核糖体肽合酶的组合生物合成研究策略，从模块定点突变、替换、插入、删除、模块“洗牌”与异源表达等角度进行了综述。

英文摘要：

Many microorganisms could use nonribosomal peptide synthetases to synthesize various lowmolecule weight peptides with complicated structures and various biological activities. Combinatorial biosynthesis is to genetically manipulate antibiotic gene clusters, through strategies like gene knock-out, replacement, recombination and heterologous expression. Using this environmentally friendly method, the pool of bioactive compounds and their derivatives can be readily generated, and the yield of natural product could be improved by genetically engineering of the antibiotic producer. This article reviews the strategies of combinatorial biosynthesis frequently utilized to engineer non-ribosomal peptides in recent years, including site-directed mutation, module insertion, deletion, shuffling and heterologous expression.