Production of a new anthraquinone compound with anti-malarial activities

March 13, 2024

Producing valuable compounds using heterologous gene expression

Researchers at the RIKEN CSRS have successfully isolated a new compound, kinanthraquinone D (KQD), with antimalarial activities by expressing the kinanthraquinone (KQ) biosynthetic gene cluster in Streptomyces lividans TK23 and revealed its biosynthetic route.

In this study, the research group focused on anthraquinone compounds with a wide range of biological activities. They cultured a large amount of S. lividans TK23 heterologously expressing the KQ biosynthetic gene cluster and its pathway specific regulator (kiqA). As the result, they successfully obtained two new compounds, kinanthraquinone C (KQC) and KQD, as well as previously known compounds KQ and kinanthraquinone B (KQB). Incubation experiments demonstrated that the precursor molecules, KQB and KQ, were converted into KQC and KQD, respectively, through biosynthesis with the endogenous enzymes of S. lividans TK23. They determined the biological activity of the resulting KQ analogs and found that KQD can inhibit the growth of malarial parasites at a half-maximal inhibitory concentration (IC50) value of 0.91 μM. Structure-activity relationship studies revealed that a carboxamide group on its side chain is essential for its antimalarial activity.

These findings suggest that the production of new natural compounds and the development of new antimalarial drugs can be expected by using the heterologous expression system of Actinomyces species.

Original article

Journal of Natural Products doi: 10.1021/acs.jnatprod.3c01076

K. Sakai, Y. Futamura, T. Nogawa, Y. Zhao, H. Koshino, H. Osada, S. Takahashi,

"Production of kinanthraquinone D with anti-malarial activity by heterologous gene expression and biotransformation in Streptomyces lividans TK23".

Contact

Shunji Takahashi; Unit Leader
Katsuyuki Sakai; Postdoctoral Researcher
Natural Product Biosynthesis Research Unit