G.K. Skryabin Institute of Biochemistry and Physiology of Microorganisms, Russian Academy of Sciences, Prospekt Nauki 5, 142290 Pushchino, Moscow Region, Russia.
Steroids. 2013 Mar;78(3):370-8. doi: 10.1016/j.steroids.2012.12.010. Epub 2013 Jan 18.
Selected actinobacteria and filamentous fungi of different taxonomy were screened for the ability to carry out regio- and stereospecific hydroxylation of lithocholic acid (LCA) at position 7β. The production of ursodeoxycholic acid (UDCA) was for the first time shown for the fungal strains of Bipolaris, Gibberella, Cunninghamella and Curvularia, as well as for isolated actinobacterial strains of Pseudonocardia, Saccharothrix, Amycolatopsis, Lentzea, Saccharopolyspora and Nocardia genera. Along with UDCA, chenodeoxycholic (CDCA), deoxycholic (DCA), cholic (CA), 7-ketodeoxycholic and 3-ketodeoxycholic acids were detected amongst the metabolites by some strains. A strain of Gibberella zeae VKM F-2600 expressed high level of 7β-hydroxylating activity towards LCA. Under optimized conditions, the yield of UDCA reached 90% at 1g/L of LCA and up to 60% at a 8-fold increased substrate loading. The accumulation of the major by-product, 3-keto UDCA, was limited by using selected biotransformation media.
不同分类的放线菌和丝状真菌被筛选出来,以研究它们在石胆酸(LCA)7β位进行区域和立体特异性羟化的能力。首次发现双极菌、镰孢菌、棒孢霉属和弯孢霉属的真菌菌株,以及假诺卡氏菌、糖丝菌属、拟无枝酸菌属、节杆菌属、游动放线菌属和诺卡氏菌属的分离放线菌菌株能够生产熊去氧胆酸(UDCA)。一些菌株在代谢物中还检测到了鹅去氧胆酸(CDCA)、脱氧胆酸(DCA)、胆酸(CA)、7-酮脱氧胆酸和 3-酮脱氧胆酸。一株玉米赤霉菌 VKM F-2600 对 LCA 具有高水平的 7β-羟化活性。在优化条件下,LCA 为 1g/L 时,UDCA 的产率达到 90%,而在底物浓度增加 8 倍时,产率达到 60%。通过使用选定的生物转化培养基,限制了主要副产物 3-酮 UDCA 的积累。