Heterologous Expression of Pseudouridimycin and Description of the Corresponding Minimal Biosynthetic Gene Cluster

被引:6
|
作者
Bohringer, Nils [1 ,2 ]
Patras, Maria A. [3 ]
Schaeberle, Till F. [1 ,2 ,3 ]
机构
[1] Justus Liebig Univ Giessen, Inst Insect Biotechnol, D-35392 Giessen, Germany
[2] German Ctr Infect Res DZIF, Partner Site Giessen Marburg Langen, D-35392 Giessen, Germany
[3] Fraunhofer Inst Mol Biol & Appl Ecol IME, Branch Bioresources, D-35392 Giessen, Germany
来源
MOLECULES | 2021年 / 26卷 / 02期
关键词
antibiotic; natural product; pseudouridimycin; PUM; heterologous expression;
D O I
10.3390/molecules26020510
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Pseudouridimycin (PUM) was recently discovered from Streptomyces sp. DSM26212 as a novel bacterial nucleoside analog that competes with UTP for access to the RNA polymerase (RNAP) active site, thereby inhibiting bacterial RNAP by blocking transcription. This represents a novel antibacterial mode of action and it is known that PUM inhibits bacterial RNAP in vitro, inhibits bacterial growth in vitro, and was active in vivo in a mouse infection model of Streptococcus pyogenes peritonitis. The biosynthetic gene cluster (BGC) was previously identified and characterized by knockout experiments. However, the minimal set of genes necessary for PUM production was not proposed. To identify the minimal BGC and to create a plug-and-play production platform for PUM and its biosynthetic precursors, several versions of a redesigned PUM BGC were generated and expressed in the heterologous host Streptomyces coelicolor M1146 under control of strong promotors. Heterologous expression allowed identification of the putative serine/threonine kinase PumF as an enzyme essential for heterologous PUM production and thus corroboration of the PUM minimal BGC.
引用
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页数:10
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