[P006] Poster

1:00 PM - 1:50 PM JST(4:00 AM - 4:50 AM UTC)

[P03-308] Transcriptome and Translatome Analysis of FK506 Biosynthesis in Streptomyces tsukubaensis NRRL 18488

○Hyeseong Kim^1,5, Namil Lee^1,2,3,4,10, Woori Kim^1,5, Ji Hun Kim^1,5, Yongjae Lee^1,5, Soonkyu Hwang^1,5, Gahyeon Kim^1,5, Qingyun Dan^3,4, Matthias Schmidt^2,3,4, Yeo Joon Yoon⁶, Suhyung Cho^1,5, Bernhard Palsson^7,8, Jay D. Keasling^2,3,4,7,9, Byung-Kwan Cho^5,10 (1. Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon (Korea), 2. California Institute for Quantitative Biosciences (QB3), University of California, Berkeley, California (USA), 3. Joint BioEnergy Institute, Emeryville, California (USA), 4. Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, California (USA), 5. KI for the BioCentury, Korea Advanced Institute of Science and Technology, Daejeon (Korea), 6. College of Pharmacy, Seoul National University, Seoul (Korea), 7. Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Lyngby (Denmark), 8. Department of Bioengineering, Department of Pediatrics, University of California San Diego, La Jolla, California (USA), 9. Department of Chemical & Biomolecular Engineering, Department of Bioengineering, University of California, Berkeley, California (USA), 10. Graduate School of Engineering Biology, Korea Advanced Institute of Science and Technology, Daejeon (Korea))

Keywords:

Streptomyces,FK506,transcriptomic analysis,translatomic analysis

Streptomyces are prolific sources of pharmaceutically important secondary metabolites, whose production is governed by complex, multi-layered regulation of biosynthetic gene clusters (BGCs). To systematically understand secondary metabolism and its regulatory mechanisms in Streptomyces, we investigated Streptomyces tsukubaensis NRRL 18488, the primary producer of the widely used immunosuppressant tacrolimus (FK506). First, we completed the sequencing of the 7.9 Mb linear genome of S. tsukubaensis, enabling accurate re-annotation of the FK506 BGC. Second, transcriptome analysis during BGC activation revealed significant transcriptional shifts from primary to secondary metabolism, particularly in genes involved in FK506 biosynthesis and lysine metabolism. Finally, ribosome profiling showed that AT-rich codons slowed translational elongation in S. tsukubaensis. Notably, significant ribosome pausing occurred at the rare TTA codon in the FK506 BGC; replacing this codon alleviated the pausing and boosted FK506 production. This comprehensive genome-scale analysis provides a deep understanding of the intricate, multi-layered regulation of secondary metabolism in Streptomyces.
This research was supported by a grant of the Korea-US Collaborative Research Fund (KUCRF), funded by the Ministry of Science and ICT and Ministry of Health & Welfare, Republic of Korea (RS-2024-00468410 to B.-K.C.), and by the KAIST Strategic Research Program (N10260074 to B.-K.C.).