AUTHOR=Zheng Yanli , Li Jie , Wang Baiyang , Han Jiamei , Hao Yile , Wang Shengchen , Ma Xiangdong , Yang Shihui , Ma Lixin , Yi Li , Peng Wenfang TITLE=Endogenous Type I CRISPR-Cas: From Foreign DNA Defense to Prokaryotic Engineering JOURNAL=Frontiers in Bioengineering and Biotechnology VOLUME=Volume 8 - 2020 YEAR=2020 URL=https://www.frontiersin.org/journals/bioengineering-and-biotechnology/articles/10.3389/fbioe.2020.00062 DOI=10.3389/fbioe.2020.00062 ISSN=2296-4185 ABSTRACT=Establishment of production platforms through prokaryotic engineering in microbial organisms would be one of the most efficient means for green chemicals and fuels production. Despite the CRISPR-based technologies have readily emerged as powerful and versatile tools for genetic manipulations, their applications are generally limited in prokaryotes, possibly owing to the large size and severe cytotoxicity of the heterogeneous Cas effectors. Nevertheless, the rich natural occurrence of CRISPR-Cas systems in many bacteria and most archaea holds great potential for endogenous CRISPR-based prokaryotic engineering. The endogenous CRISPR-Cas systems, with Type I systems forming the most abundant and diverse group, would be repurposed as genetic manipulation tools once they are identified and characterized as functional in their native hosts. This article reviews the major progress in understanding mechanisms of invading DNA immunity by Type I CRISPR-Cas and summarizes the practical applications of endogenous Type I CRISPR-based toolkits for prokaryotic engineering.