Natural products have found important applications in the pharmaceutical and agricultural sectors. In bacteria, the genes that encode the biosynthesis of natural products are often colocalized in the genome, forming biosynthetic gene clusters. It has been predicted that only 3% of natural products encoded in bacterial genomes have been discovered thus far, in part because gene clusters may be poorly expressed under laboratory conditions. Heterologous expression can help convert bioinformatics predictions into products. However, challenges remain such as gene cluster prioritization, cloning of the complete gene cluster, high level expression, product identification, and isolation of products in practical yields. Here we reviewed the literature from the past five years (January 2018 to June 2023) to identify studies that discovered natural products by heterologous expression. From the 50 studies identified, we present analyses of the rationale for gene cluster prioritization, cloning methods, biosynthetic class, source taxa, and host choice. Combined, the 50 studies led to the discovery of 63 new families of natural products, supporting heterologous expression as a promising way to access novel chemistry. However, the success rate of natural product detection varied from 11% to 32% based on four large-scale studies that were part of the reviewed literature. The low success rate makes it apparent that much remains to be improved. The potential reasons for failure and points to be considered to improve the chances of success are discussed.

中文翻译：

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通过异源表达发现细菌天然产物

天然产品在制药和农业领域有着重要的应用。在细菌中，编码天然产物生物合成的基因通常共定位于基因组中，形成生物合成基因簇。据预测，迄今为止，仅发现了细菌基因组中编码的天然产物的 3%，部分原因是基因簇在实验室条件下可能表达不佳。异源表达可以帮助将生物信息学预测转化为产品。然而，挑战仍然存在，例如基因簇优先级、完整基因簇的克隆、高水平表达、产物鉴定以及实际产量中产物的分离。在这里，我们回顾了过去五年（2018年1月至2023年6月）的文献，以确定通过异源表达发现天然产物的研究。从确定的 50 项研究中，我们分析了基因簇优先顺序、克隆方法、生物合成类别、来源分类群和宿主选择的基本原理。综合起来，这 50 项研究发现了 63 个新的天然产物家族，支持异源表达是获取新化学物质的一种有前景的方法。然而，根据综述文献中的四项大规模研究，天然产物检测的成功率从 11% 到 32% 不等。低成功率表明仍有许多地方有待改进。讨论了失败的潜在原因以及提高成功机会需要考虑的要点。