新型细菌细胞催化剂催化阿糖胞苷酰化反应的研究.docVIP

  新型细菌细胞催化剂催化阿糖胞苷酰化反 应的研究# 李晓凤1，卢志洪2，赵光磊1** 5 10 15 20 25 （1. 华南理工大学 纸浆造纸工程国家重点实验室； 2. 华南理工大学 轻工与食品学院） 摘要：阿糖胞苷（ara-C）是临床上用来治疗白血病非天然核苷，但其在应用中存在脂溶性 差、在血浆中半衰期短等缺点。利用阿糖胞苷的酰化反应可获得其单酰类衍生物，此类衍生 物已被证明较之原药具有更高的抗肿瘤活性。与酶法制备相比，利用全细胞催化剂能省去酶 分离、纯化、固定等步骤，具有制备简单，成本低的优点。利用荧光假单胞菌全细胞催化剂 能高选择性地制备阿糖胞苷 5-乙酯，区域选择性92%。对培养条件进行初步优化，发现橄 榄油为最适碳源，最适橄榄油浓度和酵母膏浓度分别为 0.5%（w/v)和 0.3%（w/v)。在该培 养条件下，阿糖胞苷 5-乙酯产率达 70.02%。 关键词：全细胞催化剂;荧光假单胞菌；阿糖胞苷；乙酸乙烯酯 中图分类号：请查阅《中国图书馆分类法》 Application of a novel bacteria cell biocatalyst in the acylation of ara-C Li Xiaofeng1, Lu Zhihong2, Zhao Guanglei1 (1. South China University of Tehchnology, State Key Lab of Pulp and Paper-making Engineering; 2. South China University of Tehchnology, College of Light Indursty and Food Sciences) Abstract: 1-β-D-Arabinofuranosylcytosine (ara-C) is a kind of unnatural nucleosides, which is used for the treatment of leukemias. However, it has some disadvantages in clinical use, such as poor lipophilicity, short half-life in human plasma, etc. An approach to resolving the problems is the preparation of its monoesters by acylation, which shows a higher bioactivity than ara-C itself. Whole-cell lipase regarded as naturally immobilized catalyst has advantages over commercial lipase since it can avoid the complicated isolation, purification, and immobilization processes which account for a large part in the lipase cost. Utilizing whole-cell lipase from Pseudomonas 30 fluorescens can efficient synthesize 5-O-acetyl 1-β-D-arabinofuranosylcytosine.The regioslectivity 92%. It was found that the optimal carbon source ,concentration of olive ,concentration of yeast extract were olive oil, 0.5%(w/v),0.3%(w/v).Under these culture conditions, the yield was 70.02% . Key words: whole-cell catalyst; Pseudomonas fluorescens; 1-β-D-arabinofuranosylcytosine; vinyl 35 acetate 基金项目：高校博士点基金资助项目（No. 200805611022）； 高校博士点基金资助项目（No. 200805611104） 作者简介：李晓凤（1977-），女，副研究员，主要从事生物技术方面的研究 通信联系人：赵光磊（1975-），男，副研究员，主要从事生物处理造纸白水方面的研究. E-mail: zhaoguanglei@scut.edu