5130-29-0Relevant articles and documents
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Schwenk et al.
, p. 549 (1943)
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Efficient Synthesis of 12-Oxochenodeoxycholic Acid Using a 12α-Hydroxysteroid Dehydrogenase from Rhodococcus ruber
Shi, Shou-Cheng,You, Zhi-Neng,Zhou, Ke,Chen, Qi,Pan, Jiang,Qian, Xiao-Long,Xu, Jian-He,Li, Chun-Xiu
supporting information, p. 4661 - 4668 (2019/09/10)
12α-Hydroxysteroid dehydrogenase (12α-HSDH) has the potential to convert cheap and readily available cholic acid (CA) to 12-oxochenodeoxycholic acid (12-oxo-CDCA), a key precursor for chemoenzymatic synthesis of the therapeutic bile acid ursodeoxycholic acid (UDCA). In this work, a native nicotinamide adenine dinucleotide (NAD+)-dependent 12α-hydroxysteroid dehydrogenase (Rr12α-HSDH) from Rhodococcus ruber was identified using a structure-guided genome mining (SSGM) approach, which is based on the structure of cofactor pocket and the conserved nicotinamide cofactor binding motif alignment. Rr12α-HSDH was heterologously overexpressed in Escherichia coli BL21 (DE3), purified and characterized. The purified Rr12α-HSDH showed a high oxidative activity of 290 U mg?1protein toward CA, with a catalytic efficiency (kcat/KM) of 5.10×103 mM?1 s?1. In a preparative biotransformation (100 mL), CA (200 mM, 80 g L?1) was efficiently converted to 12-oxo-CDCA in 1 h, with a 85% isolated yield and a space-time yield (STY) of up to 1632 g L?1 d?1. Furthermore, Rr12α-HSDH was shown to be able to catalyze the oxidation of other 12α-hydroxysteroids at high substrate loads (up to 200 mM), giving the corresponding 12-oxo-hydroxysteroids in 71%–85% yields, indicating the great potential of Rr12α-HSDH as a promising biocatalyst for the synthesis of various therapeutic bile acids. (Figure presented.).
Hydroxylation of lithocholic acid by selected actinobacteria and filamentous fungi
Kollerov,Monti,Deshcherevskaya,Lobastova,Ferrandi,Larovere,Gulevskaya,Riva,Donova
, p. 370 - 378 (2013/03/28)
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 1 g/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.
