Harnessing microorganism’s potential to produce natural compounds

April 26, 2024

Identification of novel elasnin derivatives with potent antibacterial activity

Researchers at the RIKEN CSRS isolated novel elasnin derivatives with potent antibacterial activity from an Actinomycetes strain, Streptomyces sp. RK18-A0406.

In this study, the Streptomyces sp. RK18-A0406 was engineered to express high levels of a previously uncharacterized Streptomyces antibiotic regulatory protein (SARP) family transcriptional regulator, named Syo_1.56, which successfully induced the production of secondary metabolites. The engineered Streptomyces sp. RK18-A0406 not only enhanced the production of known antimycins but also led to the discovery of 12 elasnin derivatives, with 10 of them being novel compounds. Through their work, the researchers determined the absolute stereochemistry of elasnin was to be 6S. Notably, Syo_1.56 was found to induce the expression of distant and distinct biosynthetic gene clusters (BGCs), rather than solely activating the BGC where it resides, showcasing a broad regulatory capability. The biological evaluation of the isolated elasnin derivatives revealed potent. Additionally, some of these derivatives exhibited antimalarial activity and showed potential as metallo β-lactamase (MBL) inhibitors, adding to their therapeutic significance.

This study's findings underscore the potential of leveraging transcriptional regulators like Syo_1.56 to activate dormant BGCs in Actinomycetes, paving the way for the development of novel antibacterial compounds.

Original article

Journal of Natural Products doi: 10.1021/acs.jnatprod.4c00259

I. A. Abdelhakim, Y. Futamura, Y. Asami, H. Hanaki, N. Kito, S. Masuda, A. Shibata, A. Muranaka, H. Koshino, K. Shirasu, H. Osada, J. Ishikawa, S. Takahashi,

"Expression of Syo_1.56 SARP Regulator Unveils Potent Elasnin Derivatives with Antibacterial Activity".

Contact

Shunji Takahashi; Unit Leader
Islam Adel Abdelhakim Amin; Special Postdoctoral Researcher
Natural Product Biosynthesis Research Unit