MoeH5: a natural glycorandomizer from the moenomycin biosynthetic pathway.

作者: Bohdan Ostash , Jennifer Campbell , Andriy Luzhetskyy , Suzanne Walker

DOI: 10.1111/MMI.12437

关键词: BiologyBiochemistrySecondary metabolismStreptomycesEnzymeStreptomyces ghanaensisGlutamine amidotransferaseBiosynthesisGeneticsRegulation of gene expressionGene

摘要: The biosynthesis of the phosphoglycolipid antibiotic moenomycin A attracts attention researchers hoping to develop new moenomycin-based antibiotics against multidrug resistant Gram-positive infections. There is detailed understanding most steps this biosynthetic pathway in Streptomyces ghanaensis (ATCC14672), except for ultimate stage, where a single pentasaccharide intermediate converted into set unusually modified final products. Here we report that only one gene, moeH5, encoding homologue glutamine amidotransferase (GAT) enzyme superfamily, responsible observed diversity terminally decorated moenomycins. Genetic and biochemical evidence support idea MoeH5 novel member GAT whose homologues are involved synthesis various secondary metabolites as well K O antigens bacterial lipopolysaccharide. Our results provide insights mechanism its counterparts, give us tool diversification antibiotics.

参考文章(62)
AN Kondakova, FV Toukach, SN Senchenkova, NP Arbatsky, AS Shashkov, Yu A Knirel, B Bartodziejska, K Zych, A Rozalski, Z Sidorczyk, None, New structures of the O-specific polysaccharides of Proteus. 3. Polysaccharides containing non-carbohydrate organic acids. Biochemistry. ,vol. 68, pp. 446- 457 ,(2003) , 10.1023/A:1023608231745
Howard Zalkin, [32] Glutamine amidotransferases Methods in Enzymology. ,vol. 113, pp. 263- 264 ,(1985) , 10.1016/S0076-6879(85)13035-1
Bertolt Gust, Chapter 7. Cloning and analysis of natural product pathways. Methods in Enzymology. ,vol. 458, pp. 159- 180 ,(2009) , 10.1016/S0076-6879(09)04807-1
U. SCHACHT, G. HUBER, Moenomycin. VII. Isolation and properties of further components of the antibiotic moenomycin. The Journal of Antibiotics. ,vol. 22, pp. 597- 602 ,(1969) , 10.7164/ANTIBIOTICS.22.597
FRANK L. WEISENBORN, JACQUELINE L. BOUCHARD, DOROTHY SMITH, FELIX PANSY, GIANPAOLO MAESTRONE, GENNARO MIRAGLIA, EDWARD MEYERS, The Prasinomycins: Antibiotics containing Phosphorus Nature. ,vol. 213, pp. 1092- 1094 ,(1967) , 10.1038/2131092A0
Yuriy A Knirel, Vladimir V Dashunin, Alexander S Shashkov, Nikolay K Kochetkov, Boris A Dmitriev, Irina L Hofman, None, Somatic antigens of Shigella: Structure of the O-specific polysaccharide chain of the Shigella dysenteriae type 7 lipopolysaccharide Carbohydrate Research. ,vol. 179, pp. 51- 60 ,(1988) , 10.1016/0008-6215(88)84109-0
Lu Feng, Jiang Tao, Hongjie Guo, Jianguo Xu, Yayue Li, Fedousi Rezwan, Peter Reeves, Lei Wang, Structure of the Shigella dysenteriae 7 O antigen gene cluster and identification of its antigen specific genes. Microbial Pathogenesis. ,vol. 36, pp. 109- 115 ,(2004) , 10.1016/J.MICPATH.2003.10.003
Olga G Ovchinnikova, Nina A Kocharova, Agnieszka Torzewska, Aleksandra Blaszczyk, Alexander S Shashkov, Yuriy A Knirel, Antoni Rozalski, None, Structure of the O-polysaccharide from the lipopolysaccharide of Providencia stuartii O43 containing an amide of d-galacturonic acid with l-serine Carbohydrate Research. ,vol. 340, pp. 1407- 1411 ,(2005) , 10.1016/J.CARRES.2005.03.011
Maria V. Fawaz, Melissa E. Topper, Steven M. Firestine, The ATP-grasp enzymes Bioorganic Chemistry. ,vol. 39, pp. 185- 191 ,(2011) , 10.1016/J.BIOORG.2011.08.004
Shinichiro Fuse, Hirokazu Tsukamoto, Yanqiu Yuan, Tsung-Shing Andrew Wang, Yi Zhang, Megan Bolla, Suzanne Walker, Piotr Sliz, Daniel Kahne, Functional and Structural Analysis of a Key Region of the Cell Wall Inhibitor Moenomycin ACS Chemical Biology. ,vol. 5, pp. 701- 711 ,(2010) , 10.1021/CB100048Q