- Wed Jan 28 (room reservation 16:00 JST [=UTC+09:00]), ELSI-1 105 Mishima Hall [Seminar] ELSI Seminar - Yoshiki Ochiai Yoshiki Ochiai Protein Engineering and Evolution Unit, Okinawa Institute of Science and Technology (OIST) Title: Exploring and Engineering Non-site-specific DNA/RNA Methyltransferases for Development of DNA/RNA Labeling Tools Abstract: DNA/RNA methyltransferases (MTases) hold great promise as tools for synthetic biology, enabling the modulation of methylation states and covalent labeling of nucleic acids. However, engineering of MTases remains challenging due to limited insights into their structure–function relationships. In this study, we applied sequence-based protein engineering to explore the sequence space of M.EcoGII, a DNA/RNA MTase notable for its lack of sequence specificity and dual substrate activity. Through ancestral sequence reconstruction, we developed Super RNA EcoGII methyltransferase (SUPREM), a non-site-specific RNA MTase with enhanced expression, thermostability, and RNA methylation activity compared to the M.EcoGII wild-type1. Furthermore, we identified a DNA-specific M.EcoGII homolog via exploration of sequences in a maximum likelihood tree2. Together, these studies developed SUPREM and its M.EcoGII homolog enzymes, which show promise as versatile tools for in vivo DNA and RNA methylation. 1. Ochiai, Y. et al. SUPREM: an engineered non-site-specific m6A RNA methyltransferase with highly improved efficiency. Nucleic Acids Research 52, 12158–12172 (2024). 2. Takei, Y. et al. Genome-wide chromatin recording resolves dynamic cell state changes. 2025.08.05.668773 Preprint at https://doi.org/10.1101/2025.08.05.668773 (2025). - Fri Jan 30 (room reservation 14:00 JST [=UTC+09:00]), ELSI-1 207 Seminar Room B [Study Group] Metabolism Hour - Fri Jan 30 (room reservation 15:00 JST [=UTC+09:00]), ELSI-1 207 Seminar Room B [Study Group] Protein language model hour A journal club about machine learning and proteins