Production of Kinanthraquinone D with Antimalarial Activity by Heterologous Gene Expression and Biotransformation in Streptomyces lividans TK23

被引：0

作者：

Sakai, Katsuyuki ^{[1
]}

Futamura, Yushi ^{[2
]}

Nogawa, Toshihiko ^{[3
]}

Zhao, Yuzhu ^{[1
,4
]}

Koshino, Hiroyuki ^{[3
]}

Osada, Hiroyuki ^{[2
]}

Takahashi, Shunji ^{[1
,4
]}

机构：

[1] RIKEN Ctr Sustainable Resource Sci, Nat Prod Biosynth Res Unit, Wako, Saitama 3510198, Japan

[2] REKEN Ctr Sustainable Resource Sci, Chem Resource Dev Unit, Wako, Saitama 3510198, Japan

[3] RIKEN Ctr Sustainable Resource Sci, Technol Platform Div, Mol Struct Characterizat Unit, Wako, Saitama 3510198, Japan

[4] Saitama Univ, Grad Sch Sci & Engn, Saitama, Saitama 3388570, Japan

来源：

JOURNAL OF NATURAL PRODUCTS | 2024年 / 87卷 / 04期

基金：

日本学术振兴会;

关键词：

IDENTIFICATION; CLUSTER;

D O I：

10.1021/acs.jnatprod.3c01076

中图分类号：

Q94 [植物学];

学科分类号：

071001 ;

摘要：

Two new compounds, kinanthraquinone C (1) and kinanthraquinone D (2), were isolated along with two known compounds, kinanthraquinone (3) and kinanthraquinone B (4), produced by the heterologous expression of the kiq biosynthetic gene cluster and its pathway-specific regulator, kiqA, in Streptomyces lividans TK23. The chemical structures of compounds 1 and 2 were determined using mass spectrometry and nuclear magnetic resonance analyses. To examine a biosynthetic pathway of compounds 1 and 2, incubation experiments were conducted using S. lividans TK23 to supply the compounds 3 and 4. These experiments indicated that compounds 3 and 4 were converted to compounds 2 and 1, respectively, by the endogenous enzymes of S. lividans TK23. Compounds 2, 3, and 4 had antimalarial activities at half-maximal inhibitory concentration values of 0.91, 1.2, and 15 mu M, respectively, without cytotoxicity up to 30 mu M.

引用

页码：855 / 860

页数：6