Heterologous Expression of Type II PKS Gene Cluster Leads to Diversified Angucyclines in Streptomyces albus J1074

被引:2
作者
Zhang, Xiaoting [1 ]
Zhang, Falei [1 ]
Li, Chen [1 ]
Li, Jiayi [1 ]
Xu, Xiao [1 ]
Zhu, Tianjiao [1 ]
Che, Qian [1 ]
Li, Deihai [1 ,2 ,3 ]
Zhang, Guojian [1 ,2 ,4 ]
机构
[1] Ocean Univ China, Sch Med & Pharm, Key Lab Marine Drugs, Chinese Minist Educ, Qingdao 266003, Peoples R China
[2] Qingdao Marine Sci & Technol Ctr, Lab Marine Drugs & Bioprod, Qingdao 266237, Peoples R China
[3] Ocean Univ China, Sanya Oceanog Inst, Sanya 572025, Peoples R China
[4] Marine Biomed Res Inst Qingdao, Qingdao 266101, Peoples R China
基金
中国国家自然科学基金;
关键词
heterologous expression; II PKS; marine Streptomyces; angucycline; INTERGENERIC CONJUGATION; NATURAL-PRODUCTS; BIOSYNTHESIS; ANTIBIOTICS; METABOLITES; MODE;
D O I
10.3390/md22110480
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Heterologous expression has emerged as an effective strategy in activating Streptomyces cryptic gene clusters or improving yield. Eight compounds were successfully obtained by heterologous expression of the type II PKS gene cluster spi derived from marine Streptomyces sp. HDN155000 in the chassis host Streptomyces albus J1074. The structures with absolute configurations were elucidated using extensive MS and NMR spectroscopic methods, as well as theoretical NMR calculations and electronic circular dichroism (ECD) calculations. Interestingly, compound WS009 Z (2) contains a rare thiomethyl group, angumycinone T (4) has a novel oxo-bridge formed between C12a and C4, and angumycinone X (3) showed cytotoxicity toward K562 and NCI-H446/EP cell lines.
引用
收藏
页数:13
相关论文
共 45 条
[1]   Gephyromycin, the first bridged angucyclinone, from Streptomyces griseus strain NTK 14 [J].
Bringmann, G ;
Lang, G ;
Maksimenka, K ;
Hamm, A ;
Gulder, TAM ;
Dieter, A ;
Bull, AT ;
Stach, JEM ;
Kocher, N ;
Müller, WEG ;
Fiedler, HP .
PHYTOCHEMISTRY, 2005, 66 (11) :1366-1373
[2]   SpecDis: Quantifying the Comparison of Calculated and Experimental Electronic Circular Dichroism Spectra [J].
Bruhn, Torsten ;
Schaumloeffel, Anu ;
Hemberger, Yasmin ;
Bringmann, Gerhard .
CHIRALITY, 2013, 25 (04) :243-249
[3]   Cryptic Sulfur Incorporation in Thioangucycline Biosynthesis [J].
Cao, Mingming ;
Zheng, Chengjian ;
Yang, Dong ;
Kalkreuter, Edward ;
Adhikari, Ajeeth ;
Liu, Yu-Chen ;
Rateb, Mostafa E. ;
Shen, Ben .
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2021, 60 (13) :7140-7147
[4]   Functional analyses of oxygenases in jadomycin biosynthesis and identification of JadH as a bifunctional oxygenase/dehydrase [J].
Chen, YH ;
Wang, CC ;
Greenwell, L ;
Rix, U ;
Hoffmeister, D ;
Vining, LC ;
Rohr, JR ;
Yang, KQ .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (23) :22508-22514
[5]   Tetracycline antibiotics: Mode of action, applications, molecular biology, and epidemiology of bacterial resistance [J].
Chopra, I ;
Roberts, M .
MICROBIOLOGY AND MOLECULAR BIOLOGY REVIEWS, 2001, 65 (02) :232-+
[6]   An Efficient Intergeneric Conjugation of DNA from Escherichia coli to Mycelia of the Lincomycin-Producer Streptomyces lincolnensis [J].
Du, Lei ;
Liu, Rui-Hua ;
Ying, Li ;
Zhao, Guang-Rong .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2012, 13 (04) :4797-4806
[7]   Cas12a-assisted precise targeted cloning using in vivo Cre-lox recombination [J].
Enghiad, Behnam ;
Huang, Chunshuai ;
Guo, Fang ;
Jiang, Guangde ;
Wang, Bin ;
Tabatabaei, S. Kasra ;
Martin, Teresa A. ;
Zhao, Huimin .
NATURE COMMUNICATIONS, 2021, 12 (01)
[8]   Heterologous Expression of the Nybomycin Gene Cluster from the Marine Strain Streptomyces albus subsp chlorinus NRRL B-24108 [J].
Estevez, Marta Rodriguez ;
Myronovskyi, Maksym ;
Gummerlich, Nils ;
Nadmid, Suvd ;
Luzhetskyy, Andriy .
MARINE DRUGS, 2018, 16 (11)
[9]   Novel Bioactive Paulomycin Derivatives Produced by Streptomyces albus J1074 [J].
Fernandez-De la Hoz, Jorge ;
Mendez, Carmen ;
Salas, Jose A. ;
Olano, Carlos .
MOLECULES, 2017, 22 (10)
[10]  
Frisch M. J., 2016, Gaussian 16 rev. B.01