Lovastatin/monacolin K (MK) is used as a lipid lowering drug, due to its effective hypercholesterolemic properties, comparable to synthetic statins. Lovastatin's biosynthetic pathway and gene cluster composition have been studied in depth in Aspergillus terreus. Evidence shows that the MK biosynthetic pathway and gene cluster in Monascus sp. are similar to those of lovastatin in A. terreus. Currently, research efforts have been focusing on the metabolic regulation of MK/lovastatin synthesis, and the evidence shows that a combination of extracellular and intracellular factors is essential for proper MK/lovastatin metabolism. Here, we comprehensively review the research progress on MK/lovastatin biosynthetic pathways, its synthetic precursors and inducing substances and metabolic regulation, with a view to providing reference for future research on fungal metabolism regulation and metabolic engineering for MK/lovastatin production.
In Asia, Monascus has been used in food fermentation for nearly a thousand years. It has attracted increasing attention in recent years due to its ability to produce a variety of important active substances such as monacolin K (MK) and pigments. MK is an effective drug widely used for lowering human blood cholesterol that functions by inhibiting the rate-limiting enzyme in cholesterol biosynthesis. Monascus strains, fermentation methods and fermentation conditions have significant effects on MK yield, and much research has been undertaken to obtain higher MK yields. In this paper, the research progress of Monascus strain breeding for high MK yield, medium optimization for MK production during Monascus fermentation, and optimization of fermentation process conditions are fully reviewed. This provides reference for future research on Monascus fermentation and industrial production for high-yield MK production.
Panax japonicus C. A. Mey. is a rare traditional Chinese herbal medicine that uses ginsenosides as its main active ingredient. Rice does not produce ginsenosides because it lacks a key rate-limiting enzyme (β-amyrin synthase, βAS); however, it produces a secondary metabolite, 2,3-oxidosqualene, which is a precursor for ginsenoside biosynthesis. In the present study, the P. japonicus βAS gene was transformed into the rice cultivar ‘Taijing 9’ using an Agrobacterium-mediated approach, resulting in 68 rice transgenic plants of the T0 generation. Transfer-DNA (T-DNA) insertion sites in homozygous lines of the T2 generation were determined by using high-efficiency thermal asymmetric interlaced PCR (hiTAIL-PCR) and were found to vary among the tested lines. Approximately 1–2 copies of the βAS gene were detected in transgenic rice plants. Real-time PCR and Western blotting analyses showed that the transformed βAS gene could be overexpressed and β-amyrin synthase could be expressed in rice. HPLC analysis showed that the concentration of oleanane-type sapogenin oleanolic acid in transgenic rice was 8.3–11.5 mg/100 g dw. The current study is the first report on the transformation of P. japonicus βAS gene into rice. We have successfully produced a new rice germplasm, “ginseng rice”, which produces oleanane-type sapogenin.