Mitousis Lena, Musiol-Kroll Ewa, Wohlleben Wolfgang
Interfaculty Institute for Microbiology and Infection Medicine Tübingen (IMIT), Microbiology/Biotechnology, University of Tübingen, Auf der Morgenstelle 28, 72076 Tübingen, Germany.
Cluster of Excellence, "Controlling Microbes to Fight Infections" (EXC2124), University of Tübingen, 72076 Tübingen, Germany.
Microlife. 2025 Jun 12;6:uqaf010. doi: 10.1093/femsml/uqaf010. eCollection 2025.
Actinomycetes are important producers of valuable natural products that are applied in medicine or industry. The enzymes necessary for the synthesis of those compounds are encoded in biosynthetic gene clusters (BGCs) in the genome. However, the discovery of new natural products or the improvement of production levels can be hindered by difficulties in genetic manipulation, since standard methods often do not or not efficiently work in actinomycetes. One possible explanation for this could be the presence of nucleic acid defense systems such as CRISPR-Cas. Even though there is a lot of research published about CRISPR-Cas systems in general, the knowledge about the function of CRISPR-Cas in actinomycetes is very limited. Based on sequence data it is known that CRISPR-Cas systems occur in around half of all sequenced actinobacterial genomes. Moreover, analyses of those systems have led to the discovery of new subtypes. The few examples of experimental evidence of CRISPR-Cas activity or , however, point to some special features, regarding crRNA maturation or life-cycle dependent CRISPR-Cas activity. This short review draws attention to this neglected research area and highlights the available data about CRISPR-Cas in actinomycetes.
放线菌是医学或工业中应用的有价值天然产物的重要生产者。合成这些化合物所需的酶由基因组中的生物合成基因簇（BGCs）编码。然而，由于标准方法在放线菌中往往无法有效发挥作用，基因操作的困难可能会阻碍新天然产物的发现或产量水平的提高。对此的一种可能解释是存在核酸防御系统，如CRISPR-Cas。尽管总体上已经发表了大量关于CRISPR-Cas系统的研究，但关于CRISPR-Cas在放线菌中的功能的知识非常有限。基于序列数据可知，CRISPR-Cas系统存在于约一半已测序的放线菌基因组中。此外，对这些系统的分析导致发现了新的亚型。然而，关于CRISPR-Cas活性的实验证据的少数例子表明，在crRNA成熟或生命周期依赖性CRISPR-Cas活性方面存在一些特殊特征。这篇简短的综述提请人们关注这个被忽视的研究领域，并强调了关于放线菌中CRISPR-Cas的现有数据。
