双菌多轮序列协同转化甾体制氢化可的松

建立了蓝色犁头霉AS 3．65和新月弯孢霉AS 3．4381协同多轮转化17α-羟基孕甾-4-烯-3，20-二酮-21-醋酸酯（RSA）割氢化可的松（hydrocortisone，HC）新工艺。在培养好的AS 3．65和AS 3．4381所组成的协同转化体系中，AS 3．65首先将RSA水解为脱氧皮质酮（RS），这较AS 3．4381单轮批次转化省去了RSA到RS的化学水解工序。在甾体底物RSA平均投料质量浓度为1．3g/L和1g／L的条件下，所选定的协同转化体系可分别被重复利用3轮和6轮，相应的平均产率能维持在较高水平，分别高达81．6％和85％。另外，该工艺明显减少了底物RSA投料浓度对C11位羟化的影响，并有效抑制了AS 3．4381和AS 3．65单独转化过程中出现的14α—OH—RS和11α-OH—RS副产物．

A novel process of multi-run sequence bioconversion of RSA for production of hydrocortisone with Absidia coerulea AS 3.65 and Curvularia lunata AS 3.4381

A novel process of multi-run sequence biotransformation of 17α-hydroxypregn-4-en-3,20-dione-21-acetate (RSA) to hydrocortisone (HC) was developed by active mycelia of Absidia coerulea AS 3.65 and Curvularia lunata AS 3.4381. The cooperative sequence bioconversion was efficiently operated with the cultured mycelia of AS 3.65 and AS 3.4381. RSA was hydrolyzed to RS by AS 3.65, and omitted the chemical hydrolysis step with AS 3.4381 in a single batch conversion. Moreover, a multi-run sequence conversion system with the mycelia of AS 3.65 and AS 3.4381 was reused for three or six times, and the rate of each conversion run of RSA to HC was kept at a high level, i.e., the hydroxylation at C_11-β position of RS was more than 81.6% and 85% with 1.3 g/L and 1 g/L RSA substrate concentrations, respectively. Generally, under this condition, three-run and six-run sequence bioconversion was done. In particular, the effect of RSA concentration on C_11-position hydroxylation was reduced, and the production of undesirable by-product was inhibited, i.e., on 14α-OH-RS of AS 3.4381 and on 11α-OH-RS of AS 3.65, respectively.