应用混合菌系实现右旋磷霉素手性生物转化的初步研究

Preliminary Study on the Chiral Biotransformation of Dextral-fosfomycin by Mixed Bacterial Culture

探索了一条通过混合菌系把右旋磷霉素转化为左旋磷霉素的生物转化新途径。采用"右旋磷霉素利用菌"和"左旋磷霉素抗性菌"两种筛选模型,从某制药厂土壤中筛选到了7株右旋磷霉素利用菌和6株左旋磷霉素抗性菌。将上述13株菌混合接种到以0.5%右旋磷霉素为唯一碳源的无机盐培养基中,30℃、150r/min培养3～5d,经磷霉素敏感菌生物检测、薄层层析(TLC)检测,初步确证了转化产物中存在左旋磷霉素。对右旋磷霉素的手性生物转化条件进行了初步探索,发现接种时带入少量肉汤培养基对转化有促进作用,而微量元素Co^(2-)和VO_3^-对转化没有促进作用。为在磷霉素生产中减少资源浪费和提高产量提供了理论依据。

A new approach to transform D-fosfomycin to L-fosfomycin by the catalysis of mixed bacteria was studied in this paper.Using models for screening substrate utilization bacteria and product resistance bacteria,seven D-fosfomycin utilization strains and six L-fosfomycin resistance strains were found in soil samples collected from a pharmaceutical factory. These strains were inoculated into a mineral medium supplemented with 0.5%D-fosfomycin as the sole carbon source.After incubation for 3 to 5 days at 30℃and 150rpm/min,the production of L-fosfomycin was confirmed by bioassay and Thin Layer Chromatography(TLC).Meanwhile,the conditions of chiral biotransformation were preliminarily studied. Small amounts of broth culture promoted the biotransformation of D-fosfomycin while cobaltⅡand vanadium iron had no effects.Our results provide a theoretical basis for the reducing the resource waste and increasing the production yield in the existing production procedure of FOM.