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
收藏
页数:10
相关论文
共 50 条
  • [21] Heterologous Expression Guides Identification of the Biosynthetic Gene Cluster of Chuangxinmycin, an Indole Alkaloid Antibiotic
    Xu, Xiaokun
    Zhou, Haibo
    Liu, Yang
    Liu, Xiaotong
    Fu, Jun
    Li, Aiying
    Li, Yue-zhong
    Shen, Yuemao
    Bian, Xiaoying
    Zhang, Youming
    JOURNAL OF NATURAL PRODUCTS, 2018, 81 (04): : 1060 - 1064
  • [22] Expression of the Platencin Biosynthetic Gene Cluster in Heterologous Hosts Yielding New Platencin Congeners
    Smanski, Michael J.
    Casper, Jeffrey
    Peterson, Ryan M.
    Yu, Zhiguo
    Rajski, Scott R.
    Shen, Ben
    JOURNAL OF NATURAL PRODUCTS, 2012, 75 (12): : 2158 - 2167
  • [23] Cloning and Heterologous Expression of the Vibrioferrin Biosynthetic Gene Cluster from a Marine Metagenomic Library
    Fujita, Masaki J.
    Kimura, Nobutada
    Sakai, Atsushi
    Ichikawa, Yoichi
    Hanyu, Tomohiro
    Otsuka, Masami
    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY, 2011, 75 (12) : 2283 - 2287
  • [24] Heterologous expression of pikromycin biosynthetic gene cluster using Streptomyces artificial chromosome system
    Hye-rim Pyeon
    Hee-Ju Nah
    Seung-Hoon Kang
    Si-Sun Choi
    Eung-Soo Kim
    Microbial Cell Factories, 16
  • [25] Cloning and heterologous expression of the aranciamycin biosynthetic gene cluster revealed a new flexible glycosyltransferase
    Luzhetskyy, Andriy
    Mayer, Almuth
    Hoffmann, Jens
    Pelzer, Stefan
    Holzenkaemper, Meike
    Schmitt, Bettina
    Wohlert, Sven-Eric
    Vente, Andreas
    Bechthold, Andreas
    CHEMBIOCHEM, 2007, 8 (06) : 599 - 602
  • [26] Engineered Streptomyces avermitilis Host for Heterologous Expression of Biosynthetic Gene Cluster for Secondary Metabolites
    Komatsu, Mamoru
    Komatsu, Kyoko
    Koiwai, Hanae
    Yamada, Yuuki
    Kozone, Ikuko
    Izumikawa, Miho
    Hashimoto, Junko
    Takagi, Motoki
    Omura, Satoshi
    Shin-ya, Kazuo
    Cane, David E.
    Ikeda, Haruo
    ACS SYNTHETIC BIOLOGY, 2013, 2 (07): : 384 - 396
  • [27] Heterologous expression of pikromycin biosynthetic gene cluster using Streptomyces artificial chromosome system
    Pyeon, Hye-rim
    Nah, Hee-Ju
    Kang, Seung-Hoon
    Choi, Si-Sun
    Kim, Eung-Soo
    MICROBIAL CELL FACTORIES, 2017, 16
  • [28] Identification, Heterologous Expression, and Characterization of the Tolypodiol Biosynthetic Gene Cluster through an Integrated Approach
    Back, Daniel
    O'Donnell, Timothy J.
    Axt, Kyle K.
    Gurr, Joshua R.
    Vanegas, Juan M.
    Williams, Philip G.
    Philmus, Benjamin
    ACS CHEMICAL BIOLOGY, 2023, 18 (08) : 1797 - 1807
  • [29] Heterologous Expression of Spinosyn Biosynthetic Gene Cluster in Streptomyces Species Is Dependent on the Expression of Rhamnose Biosynthesis Genes
    Zhao, Chen
    Huang, Ying
    Guo, Chao
    Yang, Bolei
    Zhang, Yan
    Lan, Zhou
    Guan, Xiong
    Song, Yuan
    Zhang, Xiaolin
    JOURNAL OF MOLECULAR MICROBIOLOGY AND BIOTECHNOLOGY, 2017, 27 (03) : 190 - 198
  • [30] Cloning, sequencing, analysis, and heterologous expression of the fredericamycin biosynthetic gene cluster from Streptomyces griseus
    Wendt-Pienkowski, E
    Huang, Y
    Zhang, J
    Li, BS
    Jiang, H
    Kwon, HJ
    Hutchinson, CR
    Shen, B
    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2005, 127 (47) : 16442 - 16452