Coordinated biosynthesis of the purine nucleoside antibiotics aristeromycin and coformycin in actinomycetes

doi:10.1128/AEM.01860-18

	Coordinated biosynthesis of the purine nucleoside antibiotics aristeromycin and coformycin in actinomycetes
	Xu, Gudan 1; Kong, Liyuan 1,2; Gong, Rong 1; Xu, Liudong 3; Gao, Yaojie 3; Jiang, Ming 3; Cai, You-Sheng 1; Hong, Kui 1; Hu, Youcai 2; Liu, Peng 1
刊名	Applied and Environmental Microbiology
	2018-11-01
卷号	84 期号:22
ISSN号	00992240
DOI	10.1128/AEM.01860-18
文献子类	Article
英文摘要	Purine nucleoside antibiotic pairs, concomitantly produced by a single strain, are an important group of microbial natural products. Here, we report a target-directed genome mining approach to elucidate the biosynthesis of the purine nucleoside antibiotic pair aristeromycin (ARM) and coformycin (COF) in Micromonospora haikouensis DSM 45626 (a new producer for ARM and COF) and Streptomyces citricolor NBRC 13005 (a new COF producer). We also provide biochemical data that MacI and MacT function as unusual phosphorylases, catalyzing an irreversible reaction for the tailoring assembly of neplanocin A (NEP-A) and ARM. Moreover, we demonstrate that MacQ is shown to be an adenosine-specific deaminase, likely relieving the potential "excess adenosine" for producing cells. Finally, we report that MacR, an annotated IMP dehydrogenase, is actually an NADPH-dependent GMP reductase, which potentially plays a salvage role for the efficient supply of the precursor pool. Hence, these findings illustrate a fine-tuned pathway for the biosynthesis of ARM and also open the way for the rational search for purine antibiotic pairs. IMPORTANCE ARM and COF are well known for their prominent biological activities and unusual chemical structures; however, the logic of their biosynthesis has long been poorly understood. Actually, the new insights into the ARM and COF pathway will not only enrich the biochemical repertoire for interesting enzymatic reactions but may also lay a solid foundation for the combinatorial biosynthesis of this group of antibiotics via a target-directed genome mining strategy.
语种	英语
出版者	American Society for Microbiology
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/266965]
专题	中国科学院上海药物研究所
通讯作者	Chen, Wenqing
作者单位	1.Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education and School of Pharmaceutical Sciences, Wuhan University, Wuhan, China; 2.State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; 3.State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China; 4.Agricultural Research Service, U.S. Department of Agriculture, National Center for Agricultural Utilization Research, Peoria; IL, United States
推荐引用方式 GB/T 7714	Xu, Gudan,Kong, Liyuan,Gong, Rong,et al. Coordinated biosynthesis of the purine nucleoside antibiotics aristeromycin and coformycin in actinomycetes[J]. Applied and Environmental Microbiology,2018,84(22).
APA	Xu, Gudan.,Kong, Liyuan.,Gong, Rong.,Xu, Liudong.,Gao, Yaojie.,...&Chen, Wenqing.(2018).Coordinated biosynthesis of the purine nucleoside antibiotics aristeromycin and coformycin in actinomycetes.Applied and Environmental Microbiology,84(22).
MLA	Xu, Gudan,et al."Coordinated biosynthesis of the purine nucleoside antibiotics aristeromycin and coformycin in actinomycetes".Applied and Environmental Microbiology 84.22(2018).