Simvastatin, a semisynthetic derivertive of lovastatin, is an important drug for the treatment of hypercholesteromia, and is traditionally prepared by direct alkylation of lovastatin. Chemical reaction conditons are very rigid, and the final product is difficult to purify, also the pressure of labor protection and environment protection is very high. Recently, with the devolpement in the research of lovastatin biosynthesis, more and more attention has been paid to simvastatin biosynthesis. This paper compared the chemical and biological routes in simvastatin production. Simvastatin could be produced by direct fermentation with combinational biosynthesis method, and could also be synthesized from monacolin J with acyltransferase LovD.
Acyltransferases ; genetics ; metabolism ; Anticholesteremic Agents ; metabolism ; Catalysis ; Escherichia coli ; genetics ; metabolism ; Fermentation ; Lovastatin ; analogs & derivatives ; biosynthesis ; Naphthalenes ; metabolism ; Simvastatin ; metabolism ; Transformation, Bacterial

ObjectiveTo investigate the feasibility of apical sodium-dependent bile salt transporter (ASBT) and asialoglycoprotein receptor (ASGPR) in the design of oral liver-targeting preparations for the treatment of hepatic alveolar echinococcosis (HAE) by measuring the expression of ASBT and ASGPR. MethodsA total of 18 male Sprague-Dawley rats were selected, among which 10 were used to establish a model of HAE (HAE group) and 8 were used as controls (normal group). Immunofluorescence assay, Western blotting, and quantitative real-time PCR were used to measure the expression distribution, protein expression level, and mRNA expression level of ASBT in the ileal tissue of HAE model rats and normal rats; the same methods were used to measure the expression level of ASGPR in the non-diseased liver tissue and the marginal zone of liver tissue lesion of HAE model rats and the liver tissue of normal rats. The t-test was used for comparison of normally distributed continuous data between two groups; a one-way analysis of variance was used for comparison between three groups, and the least significant difference t-test was used for comparison between two groups. ResultsThe results of immunofluorescence assay, Western blotting, and quantitative real-time PCR showed that compared with the normal group, the HAE group had significantly upregulated expression of ASBT in the ileal tissue (t=5309, 4.110, and 28.060, all P＜0.05) and a significantly higher expression level of ASGPR (the closer to the lesion, the higher the expression) (F=110666, 128.201, and 143.879, all P＜0.001). ConclusionASBT and ASGPR can be used as potential mediated receptors for oral liver-targeting preparations for HAE, which provides a theoretical basis for the design of oral liver-targeting preparations for the treatment of HAE.