CAJ | 학술논문

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)制氢化可的松(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1.3 g/L和1 g/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C_11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14-α-OH-RS和11-α-OH-RS副产物.
건립료람색리두매AS 3.65화신월만포매AS 3.4381협동다륜전화17α-간기잉치-4-희-3,20-이동-21-작산지(RSA)제경화가적송(hydrocortisone,HC)신공예.재배양호적AS 3.65화AS 3.4381소조성적협동전화체계중,AS 3.65수선장RSA수해위탈양피질동(RS),저교AS 3.4381단륜비차전화성거료RSA도RS적화학수해공서.재치체저물RSA평균투료질량농도위1.3 g/L화1 g/L적조건하,소선정적협동전화체계가분별피중복이용3륜화6륜,상응적평균산솔능유지재교고수평,분별고체81.6%화85%.령외,해공예명현감소료저물RSA투료농도대C_11위간화적영향,병유효억제료AS 3.4381화AS 3.65단독전화과정중출현적14-α-OH-RS화11-α-OH-RS부산물.
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.