Search Results (65)

Red yeast rice (RYR), a traditional fermented product obtained via rice fermentation with Monascus purpureus, has a millennia-long history of culinary and medicinal use in East Asia and has gained global attention as a prominent functional food ingredient for its well-recognized cholesterol-lowering properties. This review is driven by one core question: How can the dual challenges of standardizing key bioactive constituents, particularly monacolin K (MK), while eliminating the mycotoxin citrinin be addressed through biotechnological and analytical advances? This narrative review consolidates the latest research progress on RYR-derived bioactive compounds, with a specific focus on their production optimization, multifaceted health-promoting potentials, safety regulation, and application prospects in health food development. We elaborate on key advances in fermentation biotechnology and strain engineering for enhancing the yield of the core lipid-lowering component MK while eliminating the nephrotoxic mycotoxin citrinin, and comprehensively summarize the synergistic bioactivities of RYR metabolites beyond MK. The current applications of RYR in functional foods, dietary supplements, and traditional fermented products are detailed, alongside a comparison of the divergent regulatory frameworks for RYR across major global markets. Finally, we identify critical bottlenecks restricting RYR industrialization, including extreme inter-product heterogeneity and global regulatory fragmentation, and propose evidence-based future research directions to facilitate the development of safe, standardized, and effective RYR-based health foods. Full article

Red yeast rice (RYR) food supplements are widely used for cholesterol management owing to their content of monacolin K (MK), which, in its lactone form, is chemically identical to the prescription statin lovastatin. Despite their popularity, RYR products raise significant quality and safety concerns related to pronounced variability in MK content, frequent labeling non-compliance, contaminations with undeclared pharmaceutical statins, etc. The analytical differentiation between naturally produced MK and added synthetic lovastatin remains particularly challenging due to their identical chemical structures. This review provides a comprehensive overview of the chemical composition of RYR, with emphasis on monacolins, pigments, and relevant secondary metabolites, and critically summarizes current regulatory, safety, and quality issues associated with RYR-based food supplements. Furthermore, a practical, multi-level analytical strategy for product authentication is proposed. The approach integrates targeted quantification of MK and accompanying monacolins, identification of characteristic Monascus pigments as authenticity markers, gas chromatography–mass spectrometry for the detection of undeclared statins and other non-declared constituents, and proton nuclear magnetic resonance for global compositional fingerprinting. By combining complementary targeted and non-targeted techniques, this workflow enables more reliable authentication, detection of adulteration, and comprehensive quality assessment. The implementation of standardized analytical protocols is essential to improve transparency and enhance consumer safety in the rapidly expanding RYR supplement market. Full article

Background: Sleeve gastrectomy (SG) reliably reduces weight and triglycerides, but LDL-C responses are variable. In this retrospective observational study, we evaluated whether adjunctive monacolin K (red yeast rice; 3 mg/day) improves early lipid modulation after SG. Methods: In this single-center retrospective study of women only, 149 patients undergoing SG within the national KOS-BAR program were analyzed in four groups: controls without supplementation (CG, n = 62) and three supplementation cohorts receiving monacolin K for 6 months (G1 early (from week 1; n = 46), G2 delayed (months 3–9; n = 10), and G3 delayed (months 6–12; n = 31)). Outcomes included total cholesterol (TC), LDL-C, HDL, and triglycerides (TG). Missing data were imputed; mixed models for repeated measures assessed longitudinal changes. Results: From baseline to 6 months, LDL-C-C increased in the control group (CG; +21.9 mg/dL) and decreased in G1 (mean change: −11.1 mg/dL), with a significant group-by-time interaction (p < 0.001). HDL-C increased in both CG and G1, whereas triglyceride levels decreased more markedly in G1 than in CG (−36.2 vs. −19.6 mg/dL). Total cholesterol decreased in G1 (−13.4 mg/dL) and in G2 at 9 months (−22.5 mg/dL). Conclusions: In the early supplementation group, LDL-C-C levels decreased over the first 6 months after SG, whereas an increase was observed in the control group, which had significantly lower baseline LDL-C concentrations. In women undergoing SG, early postoperative monacolin K supplementation was associated with LDL-C stabilization and enhanced lipid optimization without impeding weight-loss benefits. Delayed initiation yields partial improvements, especially for TG and HDL-C. These observations underscore the need for prospective, sex-stratified studies with appropriate baseline adjustments to clarify the association between monacolin K use and postoperative lipid trajectories after SG. Full article

Recently, co-fermentation of functional medicinal plants with fungi has emerged as a promising strategy to enhance the overall quality of fermented foods. Monascus fermentation products have long been confronted with bottlenecks in both functionality and palatability, such as low monacolin K (MK) yield and poor flavor. Therefore, this study investigated the effects of co-fermenting Monascus purpureus with honeysuckle (Lonicera japonica Thunb.) on the bioactive metabolites and volatile flavor compounds of the fermented product. Through single-factor optimization, the addition of 0.8 g/L honeysuckle powder was identified as optimal, resulting in a 1.54-fold increase in MK yield compared to the control. Additionally, nine key genes were upregulated in the MK biosynthetic cluster (mokA–mokI). Co-fermentation also significantly increased the total flavonoid and polyphenol contents by 3.93-and 2.01-fold, respectively, and enhanced in vitro antioxidant activity. Gas chromatography-mass spectrometry analysis revealed that ketones, esters, and alcohols were the dominant volatile compounds. Orthogonal partial least squares-discriminant analysis identified 11 differential volatile compounds (variable importance in projection > 1), indicating a substantial shift in the flavor profile toward more desirable notes, with a reduction in undesirable aldehydes. These findings demonstrate that honeysuckle co-fermentation enhances the biofunctional properties of M. purpureus fermentation products and improves their sensory appeal, providing a viable bioprocessing strategy for developing high-value Monascus-based functional foods or ingredients. Full article

A universal HPLC method with diode array detection was developed for the separation and determination of the lactone and acid forms of monacolin K in the presence of other active ingredients (vitamins B₁, B₆, B₁₂, and folic acid) found in selected dietary supplements. The method also enables the quantitative determination of citrinin in monacolin K. Chromatographic separation was performed on an ACE 5 C18-PFP column (250 × 4.6 mm) thermostated at 25 °C. The mobile phase consisted of 0.005 M phosphate buffer (pH 2.60) and acetonitrile under linear gradient elution conditions. Detection was carried out spectrophotometrically at 230 nm for monacolin K and 325 nm for citrinin. The total run time was 28 min. The method was validated and met the acceptance criteria for specificity, linearity, sensitivity, accuracy, and precision. Linearity was achieved over a broad concentration range: 12.48–37.44 μg·mL⁻¹ for MK and 3.48–5.22 μg·mL⁻¹ for CTN. The method is sufficiently sensitive, with LOD and LOQ values of 0.91–2.85 μg·mL⁻¹ and 2.18–3.48 μg·mL⁻¹ for MK and CTN, respectively. Good precision (RSD < 0.70%) and intermediate precision (RSD < 1.33%) were observed. The accuracy of the method, expressed as percentage recovery at three concentration levels, ranged from 98.73% to 100.64%. The analysis revealed that the monacolin K content in randomly selected dietary supplements did not comply with the manufacturer’s declaration in any case. Full article

Wuyi Hongqu (WYH), also called black-skin-red-koji, which has been utilizing as a fermentation starter for more than one thousand years in China, is a symbiotic combination of Monascus spp. and Aspergillus niger formed through long-term application and domestication. In this study, the strains of Monascus purpureus and A. niger isolated from WYH samples were used to investigate their mutual influence, especially the effects on three main secondary metabolites from M. purpureus, Monascus pigments (MPs), monacolin K (MK), and citrinin (CIT), using a double-sided Petri dish (DSPD). The results showed that co-cultivation of M. purpureus and A. niger strains was favorable to increase the MPs production while inhibiting the CIT production by M. purpureus, especially when M. purpureus strains (M_1-1 or M₉) were co-cultivated with certain A. niger strains (An_1-2 or An₉), respectively, and both Monascus strains hardly produced detectable CIT. The expression levels of CIT-related genes in M. purpureus M_1-1 or M₉ were greatly restricted when co-cultivated with A. niger An_1-2 or An₉ confirmed by RT-qPCR. This study provides important insights into the selection of WYH production strains and the effects of fungal interactions. Full article

The increasing global prevalence of hyperuricemia (HUA), particularly among younger populations, underscores the urgent need for safe and effective dietary interventions. Monascus fungi, long utilized in East Asian food culture, ferment rice to produce red yeast rice (RYR), a functional food rich in monacolin K and Monascus pigments. Among these, Monascus yellow pigments (MYPs)—natural azaphilone compounds used as food additives and colorants—have shown antioxidant, anti-inflammatory, and metabolic regulatory activities. However, their potential to alleviate hyperuricemia remains unexplored. This study investigates the urate-lowering and organ-protective effects of MYPs through a combination of in vitro, in vivo, and gut microbiota analyses. MYPs exhibited significant xanthine oxidase (XOD) inhibitory activity, and molecular docking confirmed that monascin (MS) and ankaflavin (AK) competitively bind to the XOD active site. In a murine HUA model, MYPs significantly reduced serum uric acid (SUA) levels without causing hepatic or renal toxicity. Mechanistically, MYPs downregulated renal UA reabsorption transporters (URAT1, GLUT9) and upregulated the excretory transporter ABCG2, enhancing uric acid (UA) excretion. These findings highlight MYPs as promising food-derived bioactives with dual XOD inhibition and uricosuric effects, offering a novel nutraceutical strategy for hyperuricemia prevention and management. Full article

(1) Background: This study investigated changes in bioactive components and volatile compounds (VCs) during the production of red millet by comparing two varieties: Miao Xiang glutinous millet (waxy) and Jigu-42 (non-waxy). The samples were solid-state-fermented with “Red Ferment” and evaluated for bioactive components. (2) Methods: Multiple analytical methods—including principal component analysis (PCA), partial least squares-discriminant analysis (PLS-DA) and orthogonal PLS-DA (OPLS-DA), cluster analysis, and correlation analysis—were employed to systematically compare bioactive components and VCs. (3) Results: Significant varietal differences were observed: (1) Miao Xiang glutinous millet showed higher monacolin K (MK) and fatty acid contents; (2) Jigu-42 contained significantly more polyphenols; (3) linoleic acid dominated the fatty acid profiles of two varieties; and (4) a total of twenty-seven VCs were identified, including six alcohols, four aldehydes, seven ketones (corrected from duplicated count), two aromatic hydrocarbons, three heterocycles, one acid, three furans, and one ether. (4) Conclusions: The two varieties exhibited significant differences in MK, pigment profiles, fatty acid composition, polyphenol content, and volatile-compound profiles. These findings provide scientific guidance for the selection of the appropriate millet varieties in functional food production. Full article

Monascus produces various bioactive compounds, including monacolin K (MK), γ-aminobutyric acid (GABA), and Monascus pigments (MPs). Studies have shown that overexpressing genes within the MK biosynthetic cluster significantly enhances MK production. Additionally, MK synthesis in Monascus is regulated by other genes. Based on previous transcriptomic analyses conducted in our laboratory, a significant positive correlation was identified between the expression level of the GAD gene and MK production in M. pilosus. In this study, the GAD gene from M. pilosus was selected for overexpression, and a series of engineered M. pilosus strains were constructed. Among the 20 PCR-positive transformants obtained, 13 strains exhibited MK production increases of 12.84–52.50% compared to the parental strain, while 17 strains showed GABA production increases of 17.47–134.14%. To elucidate the molecular mechanisms underlying the enhanced production of MK and GABA, multi-omics analyses were performed. The results indicated that GAD overexpression likely promotes MK and GABA synthesis in M. pilosus by regulating key genes (e.g., HPD, HGD, and FAH) and metabolites (e.g., α-D-ribose-1-phosphate, β-alanine) involved in pathways such as tyrosine metabolism, phenylalanine metabolism, the pentose phosphate pathway, propanoate metabolism, and β-alanine metabolism. These findings provide theoretical insights into the regulatory mechanisms of MK and GABA biosynthesis in Monascus and suggest potential strategies for enhancing their production. Full article

Glycine betaine (GB) serves as both a methyl donor and osmoprotectant in microorganisms, facilitating growth and enhancing metabolic product yields. While the polyketide metabolites from Monascus purpureus, such as Monascus pigments (MPs) and monacolin K (MK), have been extensively studied, the effects of GB on their production and the underlying molecular mechanisms remain insufficiently explored. In this study, various concentrations of GB were added to Monascus purpureus M1 cultures, followed by RNA sequencing, RT-qPCR, differential gene expression analysis, and functional enrichment to investigate the regulatory impact of GB on polyketide metabolism. Protein–protein interaction network analysis identified key upregulated genes, including RPS15, RPS14, RPS5, NDK1, EGD2, and ATP9, particularly during the later growth phases. GB significantly upregulated genes involved in stress response, secondary metabolism, and polyketide biosynthesis. Scanning electron microscopy, HPLC, and UV-Vis spectrophotometry further confirmed that GB promoted both strain growth and polyketide production, with red pigment and MK production increasing by 120.08% and 93.4%, respectively. These results indicate that GB enhances growth and polyketide metabolism in Monascus purpureus by functioning as both a methyl donor and osmoprotectant, offering new insights into optimizing microbial polyketide production and revealing gene regulatory mechanisms by GB in Monascus purpureus. Full article

Monacolin K (MK), a secondary metabolite produced by Monascus spp. with the ability to inhibit cholesterol production, is structurally identical to lovastatin produced by Aspergillus terreus. In the lovastatin biosynthetic pathway, the polyketide synthase (PKS) encoded by lovB must work together with the enoyl reductase encoded by lovC to ensure lovastatin production. However, it is unclear whether mokA and mokE in the MK gene cluster of Monascus spp., both of which are highly homologous to lovB and lovC, respectively, also have the same functions for MK biosynthesis. In the current study, the high-yielding MK M. pilosus MS-1 was used as the research object, and it was found that the enoyl reductase domain of MokA may be non-functional due to the lack of amino acids at active sites, a function that may be compensated for by MokE in the MK synthesis pathway. Then, the mokE-deleted (ΔmokE), -complemented (ΔmokE::mokE), and -overexpressed (PgpdA-mokE) strains were constructed, and the results showed that ΔmokE did not produce MK, and ΔmokE::mokE restored MK synthesis, while the ability of PgpdA-mokE to produce MK was increased by 32.1% compared with the original strain MS-1. These results suggest that the MokA synthesized by Monascus spp. must be assisted by MokE to produce MK, just as lovastatin produced by A. terreus, which provides clues for further genetic engineering to improve the yield of MK in Monascus spp. Full article

Monascus is a fungus widely used in food fermentation. This study employed microbial technology, combined with microscopic morphological observations and ITS sequence analysis, to isolate, purify, and identify 10 strains of red yeast mold from various Monascus products. After the HPLC detection of metabolic products, the M8 strain containing the toxic substance citrinin was excluded. Using the EWM-TOPSIS model, the remaining nine safe Monascus strains were evaluated for their inhibitory activities against pancreatic lipase, α-glucosidase, α-amylase, and the angiotensin-converting enzyme. The M2 strain with the highest comprehensive scores for lowering blood sugar, blood lipids, and blood pressure was selected. Its fermentation product at a concentration of 3 mg/mL had inhibition rates of 96.938%, 81.903%, and 72.215%, respectively. The contents of the blood lipid-lowering active substance Monacolin K and the blood sugar and blood pressure-lowering active substance GABA were 18.078 mg/g and 5.137 mg/g, respectively. This strain can be utilized for the biosynthesis of important active substances such as Monacolin K and GABA, as well as for the fermentation production of safe and effective functional foods to address health issues like high blood lipids, high blood sugar, and high blood pressure in people. This study also provides insights into the use of natural fungi to produce healthy foods for combating chronic diseases in humans. Full article

Monascus, a genus of fungi known for its fermentation capability and production of bioactive compounds, such as Monascus azaphilone pigments and Monacolin K, have received considerable attention because of their potential in biotechnological applications. Understanding the genetic basis of these metabolic pathways is crucial for optimizing the fermentation and enhancing the yield and quality of these products. However, Monascus spp. are not model fungi, and knowledge of their genetics is limited, which is a great challenge in understanding physiological and biochemical phenomena at the genetic level. Since the first application of particle bombardment to explore gene function, it has become feasible to link the phenotypic variation and genomic information on Monascus strains. In recent decades, accurate gene editing assisted by genomic information has provided a solution to analyze the functions of genes involved in the metabolism and development of Monascus spp. at the molecular level. This review summarizes most of the genetic manipulation tools used in Monascus spp. and emphasizes Agrobacterium tumefaciens-mediated transformation and nuclease-guided gene editing, providing comprehensive references for scholars to select suitable genetic manipulation tools to investigate the functions of genes of interest in Monascus spp. Full article

Monascus species are known to produce various secondary metabolites with polyketide structures, including Monacolins, pigments, and citrinin. This study investigates the effects of 5-azacytidine on Monascus M1 and RP2. The dry weight, red, yellow, and orange pigment values, and Monacolin K yield of both Monascus strains were measured, and their hyphae observed through electron microscopy. The experimental group showed higher dry weights and pigment values than the control group for both strains. However, Monacolin K production increased substantially only for Monascus M1. Electron micrographs revealed surface wrinkles and large protrusions in both strains after 5-azacytidine treatment. As a potent DNA methylation-promoting agent, 5-azacytidine is very useful for epigenetic and cancer biology studies and for studying secondary metabolism in fungi. Full article

Monascus species are capable of producing various active metabolites, including monacolin K (MK) and pigments. Studies have shown that the overexpression of the mok I gene from the MK synthesis gene cluster in Monascus species can significantly increase MK production; however, the molecular mechanism has not yet been fully elucidated. Therefore, this study focused on the mok I gene of Monascus pilosus to construct overexpression strains of the mok I gene, resulting in high-yield MK production. Sixteen positive transformants were obtained, seven of which produced 9.63% to 41.39% more MK than the original strain, with no citrinin detected in any of the transformants. The qRT-PCR results revealed that the expression levels of mok I in the transformed strains TI-13, TI-24, and TI-25 increased by more than 50% compared to the original strain at various fermentation times, with the highest increase being 10.9-fold. Furthermore, multi-omics techniques were used to analyze the molecular mechanisms underlying enhanced MK production in transformed strains. The results indicated that mok I overexpression may enhance MK synthesis in M. pilosus by regulating the expression of key genes (such as MAO, HPD, ACX, and PLC) and the synthesis levels of key metabolites (such as delta-tocopherol and alpha-linolenic acid) in pathways linked to the biosynthesis of cofactors, the biosynthesis of unsaturated fatty acids, tyrosine metabolism, ubiquinone and other terpenoid-quinone biosynthesis, alpha-linolenic acid metabolism, and glycerophospholipid metabolism. These findings provide a theoretical basis for further study of the metabolic regulation of MK in Monascus species and for effectively enhancing their MK production. Full article