Department of Biomedical Science and Engineering, Konkuk University, Seoul 05029, Republic of Korea.
Department of Biological Engineering, Inha University, Incheon 22212, Republic of Korea.
Curr Opin Biotechnol. 2021 Jun;69:118-127. doi: 10.1016/j.copbio.2020.12.016. Epub 2021 Jan 11.
The heterologous expression of natural product biosynthetic gene clusters (BGCs) has traditionally been used as a genetic platform to link various natural product chemotypes to their corresponding genotypes. In recent years, heterologous expression has played an increasing role in natural products research with the advances in sequencing technologies and bioinformatics tools that allow for the rapid and systematic identification of known and cryptic BGCs from a large number of microbial genome sequences. The advances in synthetic biology have also facilitated the process of heterologous expression by providing tools for rapid cloning and engineering of BGCs to improve production yield or to activate silent BGCs. This paper summarizes the recent progress in the cloning and engineering of natural product BGCs and highlights recent examples of the heterologous expression of both known and cryptic BGCs in Streptomyces hosts, which will continue to play a pivotal role in genomics-driven natural product research.
天然产物生物合成基因簇（BGCs）的异源表达传统上被用作遗传平台，将各种天然产物化学型与其相应的基因型联系起来。近年来，随着测序技术和生物信息学工具的进步，能够快速系统地从大量微生物基因组序列中鉴定已知和隐藏的 BGCs，异源表达在天然产物研究中发挥了越来越重要的作用。合成生物学的进步也通过提供快速克隆和 BGC 工程的工具来促进异源表达的过程，以提高产量或激活沉默的 BGCs。本文总结了天然产物 BGC 克隆和工程的最新进展，并重点介绍了在链霉菌宿主中异源表达已知和隐藏 BGC 的最新实例，这将继续在基于基因组学的天然产物研究中发挥关键作用。
