Synthesis of TUDCA from Chicken Bile: Immobilized Dual-enzymatic System for Producing Artificial Bear Bile Substitute

Overview

Journal Microb Cell Fact

Publisher Biomed Central

Specialties Biotechnology
Microbiology

Date 2024 Dec 2

PMID 39623449

Authors

Tang Shijing

Pan Yinping

Yang Qiong

Lou Deshuai

Zhu Liancai

Tan Jun

Liu Shaoyong

Wang Bochu

Affiliations

Soon will be listed here.

Abstract

Bear bile, a valuable animal-derived medicinal substance primarily composed of tauroursodeoxycholic acid (TUDCA), is widely distributed in the medicinal market across various countries due to its significant therapeutic potential. Given the extreme cruelty involved in bear bile extraction, researchers are focusing on developing synthetic bear bile powder as a more humane alternative. This review presents an industrially practical and environmentally friendly process for producing an artificial substitute for bear bile powder using inexpensive and readily available chicken bile powder through an immobilized 7α-,7β-HSDH dual-enzymatic syste. Current technology has facilitated the industrial production of TUDCA from Tauodeoxycholic acid (TCDCA) using chicken bile powder. The review begins by examining the chemical composition, structure, and properties of bear bile, followed by an outline of the pharmacological mechanisms and manufacturing methods of TUDCA, covering chemical synthesis and biotransformation methods, and a discussion on their respective advantages and disadvantages. Finally, the process of converting chicken bile powder into bear bile powder using an immobilized 7α-Hydroxysteroid Dehydrogenases(7α-HSDH) with 7β- Hydroxysteroid Dehydrogenases (7β-HSDH) dual-enzyme system is thoroughly explained. The main objective of this review is to propose a comprehensive strategy for the complete synthesis of artificial bear bile from chicken bile within a controlled laboratory setting.

References

Reed A, Theriot C . Contribution of Inhibitory Metabolites and Competition for Nutrients to Colonization Resistance against by Commensal . Microorganisms. 2021; 9(2). PMC: 7918557. DOI: 10.3390/microorganisms9020371. View

Drudi Metalli V, Mancino M, Mancino A, Torrice A, Gatto M, Attili A . Bile salts regulate proliferation and apoptosis of liver cells by modulating the IGF1 system. Dig Liver Dis. 2007; 39(7):654-62. DOI: 10.1016/j.dld.2007.03.008. View

Leuschner U, Kurtz W . Treatment of primary biliary cirrhosis and cholestatic disorders with ursodeoxycholic acid. Lancet. 1987; 2(8557):508. DOI: 10.1016/s0140-6736(87)91812-5. View

Song K, Ellis E, Strom S, Chiang J . Hepatocyte growth factor signaling pathway inhibits cholesterol 7alpha-hydroxylase and bile acid synthesis in human hepatocytes. Hepatology. 2007; 46(6):1993-2002. DOI: 10.1002/hep.21878. View

FIELD F, Kam N, Mathur S . Regulation of cholesterol metabolism in the intestine. Gastroenterology. 1990; 99(2):539-51. DOI: 10.1016/0016-5085(90)91040-d. View

Ferrandi E, Bertolesi G, Polentini F, Negri A, Riva S, Monti D . In search of sustainable chemical processes: cloning, recombinant expression, and functional characterization of the 7α- and 7β-hydroxysteroid dehydrogenases from Clostridium absonum. Appl Microbiol Biotechnol. 2011; 95(5):1221-33. DOI: 10.1007/s00253-011-3798-x. View

Larusso N, Korman M, Hoffman N, Hofmann A . Dynamics of the enterohepatic circulation of bile acids. Postprandial serum concentrations of conjugates of cholic acid in health, cholecystectomized patients, and patients with bile acid malabsorption. N Engl J Med. 1974; 291(14):689-92. DOI: 10.1056/NEJM197410032911401. View

Nagy R, van Montfoort A, Dikkers A, van Echten-Arends J, Homminga I, Land J . Presence of bile acids in human follicular fluid and their relation with embryo development in modified natural cycle IVF. Hum Reprod. 2015; 30(5):1102-9. DOI: 10.1093/humrep/dev034. View

Yang Q, Li L, Wang B, Zhu L, Tan J . Modifying the Microenvironment of Epoxy Resin to Improve the Activity of Immobilized 7α-Hydroxysteroid Dehydrogenases. Appl Biochem Biotechnol. 2020; 193(4):925-939. DOI: 10.1007/s12010-020-03473-w. View

10.

Brevini T, Maes M, Webb G, John B, Fuchs C, Buescher G . FXR inhibition may protect from SARS-CoV-2 infection by reducing ACE2. Nature. 2022; 615(7950):134-142. PMC: 9977684. DOI: 10.1038/s41586-022-05594-0. View

11.

Tandon P, Rowe B, Vandermeer B, Bain V . The efficacy and safety of bile Acid binding agents, opioid antagonists, or rifampin in the treatment of cholestasis-associated pruritus. Am J Gastroenterol. 2007; 102(7):1528-36. DOI: 10.1111/j.1572-0241.2007.01200.x. View

12.

Zahoor B, Liu X, Wu P, Sun W, Jia X, Lv Z . Activity pattern study of Asiatic black bear (Ursus thibetanus) in the Qinling Mountains, China, by using infrared camera traps. Environ Sci Pollut Res Int. 2021; 28(20):25179-25186. DOI: 10.1007/s11356-020-12325-3. View

13.

SHEFER S, Kren B, Salen G, Steer C, Nguyen L, Chen T . Regulation of bile acid synthesis by deoxycholic acid in the rat: different effects on cholesterol 7 alpha-hydroxylase and sterol 27-hydroxylase. Hepatology. 1995; 22(4 Pt 1):1215-21. DOI: 10.1016/0270-9139(95)90631-2. View

14.

Sackmann M, Pauletzki J, Aydemir U, Holl J, Sauerbruch T, Hasford J . Efficacy and safety of ursodeoxycholic acid for dissolution of gallstone fragments: comparison with the combination of ursodeoxycholic acid and chenodeoxycholic acid. Hepatology. 1991; 14(6):1136-41. View

15.

Tilles G, Wallach D, Taieb A . Topical therapy of atopic dermatitis: controversies from Hippocrates to topical immunomodulators. J Am Acad Dermatol. 2007; 56(2):295-301. DOI: 10.1016/j.jaad.2006.09.030. View

16.

Denk G, Maitz S, Wimmer R, Rust C, Invernizzi P, Ferdinandusse S . Conjugation is essential for the anticholestatic effect of NorUrsodeoxycholic acid in taurolithocholic acid-induced cholestasis in rat liver. Hepatology. 2010; 52(5):1758-68. DOI: 10.1002/hep.23911. View

17.

Rao A, Haywood J, Craddock A, Belinsky M, Kruh G, Dawson P . The organic solute transporter alpha-beta, Ostalpha-Ostbeta, is essential for intestinal bile acid transport and homeostasis. Proc Natl Acad Sci U S A. 2008; 105(10):3891-6. PMC: 2268840. DOI: 10.1073/pnas.0712328105. View

18.

Xu Y, Yang L, Zhao S, Wang Z . Large-scale production of tauroursodeoxycholic acid products through fermentation optimization of engineered Escherichia coli cell factory. Microb Cell Fact. 2019; 18(1):34. PMC: 6368744. DOI: 10.1186/s12934-019-1076-2. View

19.

Li L, Liu C, Liu M, Shi L, Liu Q, Guan H . Taurochenodeoxycholic acid induces apoptosis of fibroblast-like synoviocytes. Eur J Pharmacol. 2013; 706(1-3):36-40. DOI: 10.1016/j.ejphar.2013.02.051. View

20.

Ying J, Dai S, Fu R, Hong J, Dai C, Jin Q . Effect of ursodeoxycholic acid on gallstone formation after bariatric surgery: An updated meta-analysis. Obesity (Silver Spring). 2022; 30(6):1170-1180. DOI: 10.1002/oby.23427. View