7β-Hydroxysteroid dehydrogenases (7β-HSDHs) play an important role in the enzymatic synthesis of ursodeoxycholic acid (UDCA), which is a value-added compound with a range of pharmacological activities. Since the cofactor NADH is much cheaper than NADPH, the production of UDCA using an NADH-dependent 7β-HSDH has better prospects than that using an NADPH-dependent 7β-HSDH. However, a major bottleneck in UDCA biosynthesis is the poor catalytic activity of the current NADH-dependent 7β-HSDHs. In this work, a new and natively NADH-dependent Rs 7β-HSDH from Roseococcus sp. was identified, which showed a high specific activity of 63.3 U mg −1 protein toward 7-oxo-lithocholic acid, with a catalytic efficiency ( k cat / K M ) of 515 mM –1 s –1 . In a preparative biotransformation (100-mL scale) using Rs 7β-HSDH and an NAD + -dependent 7α-HSDH, with O 2 /NOX and HCOO − /FDH systems for the regeneration of cofactors (NAD + and NADH), 25 mM chenodeoxycholic acid was completely converted to UDCA in one-pot two-step cascade, with an 80% isolated yield and a total turnover number (TTN) of 6586 for Rs 7β-HSDH. The environmental factor ( E -factor) of this process was 8.37 when water was excluded, much lower than those obtained from other processes reported so far, indicating a great potential of this Rs 7β-HSDH for more sustainable and cleaner enzymatic production of UDCA.
Xue Bai,Zhiguang Duan,Jianjun Deng,Zhuo Zhang,Rongzhan Fu,Chenhui Zhu,Daidi Fan
Introduction Dysbiosis of the gut microbiota is emerging as a pivotal factor in the pathogenesis of colorectal cancer (CRC). Ginsenoside Rh4 (Rh4) is an active compound isolated from ginseng with beneficial effects in modulating intestinal inflammation and gut microbiota dysbiosis, but how Rh4 regulates the gut microbiota to alleviate CRC remains underexplored. Objectives We investigated the impact of Rh4 on CRC and the mechanism of its action in inhibiting CRC via modulation of gut microbiota. Methods We used the AOM/DSS model and employed transcriptomics, genomics and metabolomics techniques to explore the inhibitory impact of Rh4 on CRC. Furthermore, we employed experiments involving antibiotic treatment and fecal microbiota transplantation (FMT) to investigate the role of the gut microbiota. Finally, we elucidated the pivotal role of key functional bacteria and metabolites regulated by Rh4 in CRC. Results Our research findings indicated that Rh4 repaired intestinal barrier damage caused by CRC, alleviated intestinal inflammation, and inhibited the development of CRC. Additionally, Rh4 inhibited CRC in a gut microbiota-dependent manner. Rh4 increased the diversity of gut microbiota, enriched the probiotic Akkermansia muciniphila ( A. muciniphila ), and alleviated gut microbiota dysbiosis caused by CRC. Subsequently, Rh4 regulated A. muciniphila -mediated bile acid metabolism. A. muciniphila promoted the production of UDCA by enhancing the activity of 7α-hydroxysteroid dehydrogenase (7α-HSDH). UDCA further activated FXR, modulated the TLR4-NF-κB signaling pathway, thus inhibiting the development of CRC. Conclusion Our results confirm that Rh4 inhibits CRC in a gut microbiota-dependent manner by modulating gut microbiota-mediated bile acid metabolism and promoting the production of UDCA, which further activates the FXR receptor and regulates the TLR4-NF-κB signaling pathway. Our results confirm that Rh4 has the potential to be used as a modulator of gut microbiota for preventing and treatment of CRC.
Bio-based surfactants derived from carbohydrates have attracted increasing attention due to their environmental friendliness, biodegradability, and biological functions. In this study, we synthesized a novel class of maltotriose acylhydrazone surfactants with different alkyl chain lengths (6–14 carbons) using a simple and efficient three-step protocol. We characterized their structure, surface activity, aggregation behavior, foaming properties, and emulsion stability. We found that these surfactants had high hydrophilicity, low toxicity, and good emulsifying and foaming abilities. We also investigated their potential as drug delivery vehicles for ursodeoxycholic acid (UDCA), a drug for primary biliary cholangitis (PBC). We prepared UDCA-loaded niosomes with these surfactants and evaluated their drug entrapment efficiency, in vitro drug release, and in vivo therapeutic effect in a mouse model of PBC. We demonstrated that these niosomes could efficiently encapsulate and deliver UDCA, resulting in improved liver function and reduced inflammation. Our results suggest that maltotriose acylhydrazone surfactants are promising candidates for bio-based surfactants and drug delivery systems.
危险品化学品经营许可证（带存储）