With the rapidly growing number of sequenced microbial (meta)genomes, enormous cryptic natural product (NP) biosynthetic gene clusters (BGCs) have been identified, which are regarded as a rich reservoir for novel drug discovery. A series of powerful tools for engineering BGCs has accelerated the discovery and development of pharmaceutically active NPs. Here, we describe recent advances in the strategies for BGCs manipulation, which are driven by emerging technologies, including efficient DNA recombination systems, versatile CRISPR/Cas9 genome editing tools and diverse DNA assembly methods. We further discuss how these approaches could be used for genome mining studies and industrial strain improvement.

随着测序的微生物（元）基因组数量的快速增长，已经确定了巨大的隐秘天然产物（NP）生物合成基因簇（BGC），它们被认为是新药发现的丰富资源库。用于工程BGC的一系列强大工具加快了药物活性NP的发现和开发。在这里，我们描述了BGC操作策略的最新进展，这些进展由新兴技术驱动，包括有效的DNA重组系统，通用的CRISPR / Cas9基因组编辑工具和多种DNA组装方法。我们将进一步讨论如何将这些方法用于基因组挖掘研究和工业菌株改良。