A LuxR family transcriptional regulator AniF promotes the production of anisomycin and its derivatives in Streptomyces hygrospinosus var.beijingensis  

作　　者：Jufang Shen Lingxin Kong Yan Li Xiaoqing Zheng Qing Wang Weinan Yang Zixin Deng Delin You 

机构地区：[1]State Key Laboratory of Microbial Metabolism,Joint International Research Laboratory of Metabolic and Developmental Sciences,School of Life Sciences&Biotechnology,Shanghai Jiao Tong University,Shanghai,China [2]Department of Immunology,Hebei Medical University,Shijiazhuang,Hebei,China

出　　处：《Synthetic and Systems Biotechnology》2019年第1期40-48,共9页合成和系统生物技术（英文）

基　　金：the National Natural Science Foundation of China(31630002,31700029,31770038,31470183,21661140002 and 31170085);the Ministry of Science and Technology,China;Shanghai Pujiang Program from the Shanghai Municipal Council of Science and Technology(12PJD021);China Postdoctoral Science Foundation(2017M620151).

摘　　要：The protein synthesis inhibitor anisomycin features a unique benzylpyrrolidine system and exhibits potent selective activity against pathogenic protozoa and fungi.It is one of the important effective components in Agricultural Antibiotic120,which has been widely used as naturally-originated agents for treatment of crop decay in China.The chemical synthesis of anisomycin has recently been reported,but the complex process with low productivity made the biosynthesis still to be a vital mainstay in efforts.The biosynthetic gene cluster(BGC)of anisomycin in Streptomyces hygrospinosus var.beijingensis has been identified in our previous work,while poor understanding of the regulatory mechanism limited the yield enhancement via regulation engineering of S.hygrospinosus var.beijingensis.In this study here,we characterized AniF as an indispensable LuxR family transcriptional regulator for the activation of anisomycin biosynthesis.The genetic manipulations of aniF and the real-time quantitative PCR(RT-qPCR)revealed that it positively regulated the transcription of the anisomycin BGC.Moreover,the overexpression of aniF contributed to the improvement of the production of anisomycin and its derivatives.Dissection of the mechanism underlying the function of AniF revealed that it directly activated the transcription of the genes aniR-G involved in anisomycin biosynthesis.Especially,one AniF-binding site in the promoter region of aniR was identified by DNase I footprinting assay and an inverted repeat sequence(5′-GGGC-3′)composed of two 4-nt half sites in the protected region was found.Taken together,our systematic study confirmed the positive regulatory role of AniF and might facilitate the future construction of engineering strains with high productivity of anisomycin and its derivatives.

关 键 词：ANISOMYCIN Agricultural Antibiotic120 BIOSYNTHESIS AniF LuxR regulator STREPTOMYCES 

分 类 号：O62[理学—有机化学]