# CRISPR-Cas in actinomycetes: still a lot to be discovered

## TL;DR

This paper reviews the limited understanding of CRISPR-Cas systems in actinomycetes, which are important for producing natural products in medicine and industry.

## Contribution

The paper highlights the under-researched role of CRISPR-Cas systems in actinomycetes and identifies new subtypes based on sequence data.

## Key findings

- CRISPR-Cas systems are present in about half of sequenced actinobacterial genomes.
- In silico analysis has revealed new CRISPR-Cas subtypes in actinomycetes.
- Experimental evidence suggests unique features in crRNA maturation and life-cycle dependent activity.

## Abstract

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, in silico analyses of those systems have led to the discovery of new subtypes. The few examples of experimental evidence of CRISPR-Cas activity in vivo or in vitro, 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.

There is only very limited knowledge about the functions of CRISPR-Cas (immunity and beyond) in the important group of natural product producing actinomycetes