具有产生安莎类抗生素潜能的放线菌的分子筛选论文.docVIP

　　具有产生安莎类抗生素潜能的放线菌的分子筛选论文 武临专 张会图 韩锋 高群杰 孙桂芝 王以光 【摘要】 目的 建立一种高通量筛选具有产生安莎类抗生素潜能的放线菌的分子筛选方法。原理 3氨基5羟基苯甲酸(AHBA)是安莎类抗生素生物合成的前体。在通过氨基莽草酸途径生物合成AHBA的过程中，AHBA合酶是催化5氨基3脱氢5脱氧莽草酸形成AHBA的一个特异性关键酶。AHBA合酶基因的存在可以作为放线菌菌株具有合成安莎类抗生素能力的一个必要而非充分的条件。AHBA合酶基因高度保守.freelycins are characterized by a benzenic or naphthalenic quinoid based chromophore ophore ide linkage (Fig.1). The chromophore is generated from a mC7N unit derived from 3amino5hydroxybenzoic acid (AHBA) via aminoshikimate pathaining part of the chromophore, and the ansa bridge are polyketide derived.Fig.1 All ansamycins use AHBA as the starter unit for their biosynthesis Ansamycins shopicin, a semisynthetic derivative of rifamycin produced by Amycolatopsis mediterranei, is one of the most effective clinical treatments of mycobacterial infection. 17allylaminodemethoxygeldanamycin (17AAG), a semisynthetic derivative of geldanamycin produced by Strepromyces hygroscopicus, is currently under clinical trials for tumor treatment［1,2］. Ansamycins are also potential antiviral agents. For example, rifamycin could block the RNAdependent DNA polymerases of retroviruses, geldanamycin could inhibit the replication of Herpes Simplex Virus type 1 (HSV1) in vitro［3］. Screening of novel ansamycins (and their producers) is of great importance in discovering promising drugcandidates or lead pounds ycins produced by streptomyces strains ycins and cytotrienin A, both of them shoor activities［4～7］. Some novel ansamycins eans of chemical and/or biological modifications of knoycins［8］. Up to noost natural ansamycins are discovered by activitybased screening of microbial (especially, actinomycetes) fermentation and extraction of products. That is,.freelodel ycins, their obvious disadvantages include: ① the limitations of the fermentation condition and the minimal bioactivity detection lead to missing the potential ansamycin in the initial screening; ② the structure determination plexity of numerous related chemistry resulted i