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Journal of Fungi (Basel, Switzerland) Dec 2020, a filamentous fungus known for its fermentation of red yeast rice, produces the metabolite monacolin K used in statin drugs to inhibit cholesterol biosynthesis. In...
, a filamentous fungus known for its fermentation of red yeast rice, produces the metabolite monacolin K used in statin drugs to inhibit cholesterol biosynthesis. In this study, we show that active cultures of CBS 109.07, independent of secondary metabolites, use the mechanism of cholesterol assimilation to lower cholesterol in vitro. We describe collection, extraction, and gas chromatography-flame ionized detection (GC-FID) methods to quantify the levels of cholesterol remaining after incubation of CBS 109.07 with exogenous cholesterol. Our findings demonstrate that active growing CBS 109.07 can assimilate cholesterol, removing 36.38% of cholesterol after 48 h of incubation at 37 °C. The removal of cholesterol by resting or dead CBS 109.07 was not significant, with cholesterol reduction ranging from 2.75-9.27% throughout a 72 h incubation. Cholesterol was also not shown to be catabolized as a carbon source. Resting cultures transferred from buffer to growth media were able to reactivate, and increases in cholesterol assimilation and growth were observed. In growing and resting phases at 24 and 72 h, the production of the mycotoxin citrinin was quantified via high-performance liquid chromatography-ultraviolet (HPLC-UV) and found to be below the limit of detection. The results indicate that CBS 109.07 can reduce cholesterol content in vitro and may have a potential application in probiotics.
PubMed: 33317087
DOI: 10.3390/jof6040352 -
Current Microbiology May 2024The fungus Monascus is a well-known source of secondary metabolites with interesting pharmaceutical and nutraceutical applications. In particular, Monascus pigments...
The fungus Monascus is a well-known source of secondary metabolites with interesting pharmaceutical and nutraceutical applications. In particular, Monascus pigments possess a wide range of biological activities (e.g. antimicrobial, antioxidant, anti-inflammatory or antitumoral). To broaden the scope of their possible application, this study focused on testing Monascus pigment extracts as potential photosensitizing agents efficient in antimicrobial photodynamic therapy (aPDT) against bacteria. For this purpose, eight different extracts of secondary metabolites from the liquid- and solid-state fermentation of Monascus purpureus DBM 4360 and Monascus sp. DBM 4361 were tested against Gram-positive and Gram-negative model bacteria, Bacillus subtilis and Escherichia coli and further screened for ESKAPE pathogens, Staphylococcus aureus and Pseudomonas aeruginosa. To the bacterial culture, increasing concentration of extracts was added and it was found that all extracts showed varying antimicrobial activity against Gram-positive bacteria in dark, which was further increased after irradiation. Gram-negative bacteria were tolerant to the extracts' exposure in the dark but sensitivity to almost all extracts that occurred after irradiation. The Monascus sp. DBM 4361 extracts seemed to be the best potential candidate for aPDT against Gram-positive bacteria, being efficient at low doses, i.e. the lowest total concentration of Monascus pigments exhibiting aPDT effect was 3.92 ± 1.36 mg/L for E. coli. Our results indicate that Monascus spp., forming monascuspiloin as the major yellow pigment and not-forming mycotoxin citrinin, is a promising source of antimicrobials and photoantimicrobials.
Topics: Monascus; Anti-Bacterial Agents; Mycelium; Microbial Sensitivity Tests; Photosensitizing Agents; Biological Products; Gram-Positive Bacteria; Complex Mixtures; Pigments, Biological; Photochemotherapy
PubMed: 38771359
DOI: 10.1007/s00284-024-03725-6 -
Foods (Basel, Switzerland) Jul 2020The prevention and treatment of chronic inflammation using food-derived compounds are desirable from the perspectives of marketing and safety. pigments, widely used as...
The prevention and treatment of chronic inflammation using food-derived compounds are desirable from the perspectives of marketing and safety. pigments, widely used as food additives, can be used as a chronic inflammation treatment. Orange pigments were produced by submerged fermentation in a 5 L bioreactor, and multiple orange pigment derivatives with anti-inflammatory activities were synthesized using aminophilic reaction. A total of 41 types of pigment derivatives were produced by incorporating amines and amino acids into the orange pigments. One derivative candidate that inhibited nitric oxide (NO) production in Raw 264.7 cells and exhibited low cell cytotoxicity was identified via in vitro assay. The 2-amino-4 picoline derivative inhibited NO production of 48.4%, and exhibited cell viability of 90.6%. Expression of inducible NO synthase, an important enzyme in the NO synthesis pathway, was suppressed by such a derivative in a dose-dependent manner. Therefore, this derivative has potential as a functional food colorant with anti-inflammatory effects.
PubMed: 32630165
DOI: 10.3390/foods9070858 -
Natural Product Reports Apr 2019Covering: up to June 2018 Understanding the biosynthetic mechanisms that generate the astounding structural complexity and variety of fungal secondary metabolites (FSMs)... (Review)
Review
Covering: up to June 2018 Understanding the biosynthetic mechanisms that generate the astounding structural complexity and variety of fungal secondary metabolites (FSMs) remains a challenge. As an example, the biogenesis of the Monascus azaphilone pigments (MonAzPs) has remained obscure until recently despite the significant medical potential of these metabolites and their long history of widespread use as food colorants. However, a considerable progress has been made in recent years towards the elucidation of MonAzPs biosynthesis in various fungi. In this highlight, we correlate a unified biosynthetic pathway with the diverse structures of the 111 MonAzPs congeners reported until June 2018. We also discuss the origins of structural diversity amongst MonAzPs analogues and summarize new research directions towards exploring novel MonAzPs. The case of MonAzPs illuminates the various ways that FSMs metabolic complexity emerges by the interplay of biosynthetic pathway determinism with metabolic and chemical serendipity.
Topics: Food Additives; Food Coloring Agents; Metabolic Networks and Pathways; Molecular Structure; Monascus; Multigene Family; Pigments, Biological; Secondary Metabolism
PubMed: 30484470
DOI: 10.1039/c8np00060c -
Frontiers in Microbiology 2022pigments (MPs) have been used in the food industry for more than 2,000 years and are known for their safety, bold coloring, and physiological activity. MPs are mainly...
pigments (MPs) have been used in the food industry for more than 2,000 years and are known for their safety, bold coloring, and physiological activity. MPs are mainly yellow (YMPs), orange (OMPs), and red (RMPs). In this study, a mutant strain H14 with high production of water-soluble YMPs (WSYMPs, at 370 nm) was generated instead of primary YMPs ( at 420 nm), OMPs ( at 470 nm), and RMPs ( at 510 nm) produced by the parent strain LQ-6 through dual mutagenesis of atmospheric and room-temperature plasma and heavy ion beam irradiation (HIBI), producing 22.68 U/ml extracellular YMPs and 10.67 U/ml intracellular YMPs. WSYMP production was increased by 289.51% in optimal conditions after response surface methodology was applied in submerged fermentation. Application of combined immobilized fermentation and extractive fermentation improved productivity to 16.89 U/ml/day, 6.70 times greater than with conservative submerged fermentation. The produced WSYMPs exhibited good tone stability to environmental factors, but their pigment values were unstable to pH, light, and high concentrations of Ca, Zn, Fe, Cu, and Mg. Furtherly, the produced exYMPs were identified as two yellow monascus pigment components (monascusone B and CHNOS) by UHPLC-ESI-MS. This strategy may be extended to industrial production of premium WSYMPs using .
PubMed: 35756045
DOI: 10.3389/fmicb.2022.914828 -
Journal of Basic Microbiology Apr 2024In eukaryotes, methylation of histone H3 at lysine 4 (H3K4me) catalyzed by the complex of proteins associated with Set1 (COMPASS) is crucial for the transcriptional...
In eukaryotes, methylation of histone H3 at lysine 4 (H3K4me) catalyzed by the complex of proteins associated with Set1 (COMPASS) is crucial for the transcriptional regulation of genes and the development of organisms. In Monascus, the functions of COMPASS in establishing H3K4me remain unclear. This study first identified the conserved COMPASS core subunits MpSet1 and MpSwd3 in Monascus purpureus and confirmed their roles in establishing H3K4me2/3. Loss of MpSet1 and MpSwd3 resulted in slower growth and development and inhibited the formation of cleistothecia, ascospores, and conidia. The loss of these core subunits also decreased the production of extracellular and intracellular Monascus pigments (MPs) by 94.2%, 93.5%, 82.7%, and 82.5%, respectively. In addition, RNA high-throughput sequencing and quantitative real-time polymerase chain reaction (qRT-PCR) showed that the loss of MpSet1 and MpSwd3 altered the expression of 2646 and 2659 genes, respectively, and repressed the transcription of MPs synthesis-related genes. In addition, the ΔMpset1 and ΔMpswd3 strains demonstrated increased sensitivity to cell wall stress with the downregulation of chitin synthase-coding genes. These results indicated that the COMPASS core subunits MpSet1 and MpSwd3 help establish H3K4me2/3 for growth and development, spore formation, and pigment synthesis in Monascus. These core subunits also assist in maintaining cell wall integrity.
Topics: Monascus; Fermentation; Pigments, Biological
PubMed: 38362934
DOI: 10.1002/jobm.202300686 -
Applied Biochemistry and Biotechnology Dec 2022Monascus species are the producers of Monascus azaphilone pigments (MonAzPs) and lipid-lowering component Monacolin K, which have been widely used as food colorant and...
Monascus species are the producers of Monascus azaphilone pigments (MonAzPs) and lipid-lowering component Monacolin K, which have been widely used as food colorant and health products. In this study, silent information regulator 2 (Sir2) homolog (MrSir2) was characterized, and its impacts on the development and MonAzPs production of Monascus ruber were evaluated. Enzyme activity test in vitro showed that MrSir2 was an NAD-dependent histone deacetylase. Compared to WT, Δmrsir2 strain accumulated more acetylated lysine residues of histone H3 subunit during its vegetative growth phase, and it exhibited accelerated mycelial aging, more spores, increased resistance to oxidative stress, and more MonAzPs production. RNA-Seq-based transcriptome analysis revealed that MrSir2 mainly regulated the gene expression in macromolecular metabolism such as carbohydrates, proteins, and nucleotides, as well as genes encoding cell wall synthesis and cell membrane component, indicating that MrSir2 probably facilitates the metabolic transition from the primary growth phase to the mycelial aging. Taken together, MrSir2 mainly targets H3 subunit at the vegetative growth phase and affects the development of M. ruber and MonAzPs production.
Topics: Monascus; Pigments, Biological; Benzopyrans
PubMed: 35802237
DOI: 10.1007/s12010-022-04030-3 -
Applied Microbiology and Biotechnology Nov 2022Monascus azaphilones (MAs) have been extensively applied as natural food coloring agents. MAs are classified into three categories: yellow MAs (YMAs), orange MAs (OMAs),...
Monascus azaphilones (MAs) have been extensively applied as natural food coloring agents. MAs are classified into three categories: yellow MAs (YMAs), orange MAs (OMAs), and red MAs with various biological activities. However, the exact biosynthetic mechanism of OMAs and YMAs are not thoroughly elucidated. Firstly, we identified four DNA-binding residues of transcription factor MrPigB and constructed a multi-site saturation mutagenesis library of MrPigB. Then, comparative metabolite and gene expression of the mutants revealed that two oxidoreductases MrPigE and MrPigF were responsible for the formation of YMAs and OMAs. Finally, the in vitro and in vivo assays demonstrated the opposite roles of MrPigE and MrPigF in conversion of OMAs to YMAs. To our knowledge, this is the first report of a binary oxidoreductase system for dynamic regulation of fungal secondary metabolite biosynthesis. Broadly, our work also demonstrates the transcription factor engineering strategy for elucidating the biosynthetic pathway of secondary metabolite. KEY POINTS: • MrPigE converts orange Monascus azaphilones to yellow Monascus azaphilones • MrPigF oxidizes intermediates to afford orange Monascus azaphilones • MrPigE and MrPigF constitute a binary system in Monascus azaphilones biosynthesis.
Topics: Monascus; Oxidoreductases; Pigments, Biological; Transcription Factors
PubMed: 36221033
DOI: 10.1007/s00253-022-12219-z -
Food Chemistry May 2024Monascus species are functional fermentation fungi with great potential for selenium (Se) supplementation. This study investigated the effects of Se bio-fortification on...
Monascus species are functional fermentation fungi with great potential for selenium (Se) supplementation. This study investigated the effects of Se bio-fortification on the growth, morphology, and biosynthesis of Monascus ruber M7. The results demonstrated a significant increase in the yield of orange and red Monascus pigments (MPs) in red yeast rice (RYR) by 38.52% and 36.57%, respectively, under 20 μg/mL of selenite pressure. Meanwhile, the production of citrinin (CIT), a mycotoxin, decreased from 244.47 μg/g to 175.01 μg/g. Transcriptome analysis revealed significant upregulation of twelve genes involved in MPs biosynthesis, specifically MpigE, MpigF, and MpigN, and downregulation of four genes (mrr3, mrr4, mrr7, and mrr8) associated with CIT biosynthesis. Additionally, three genes encoding cysteine synthase cysK (LogFC = 1.6), methionine synthase metH (LogFC = 2.2), and methionyl-tRNA synthetase metG (LogFC = 1.8) in selenocompound metabolism showed significantly upregulated. These findings provide insights into Se biotransformation and metabolism in filamentous fungi.
PubMed: 38843715
DOI: 10.1016/j.foodchem.2024.139740 -
Foods (Basel, Switzerland) Apr 2023red pigments (MRPs) are mainly used as natural food colorants; however, their application is limited due to their poor stability. To expand their areas of application,...
red pigments (MRPs) are mainly used as natural food colorants; however, their application is limited due to their poor stability. To expand their areas of application, we investigated the binding constants and capacity of MRPs to whey protein isolate (WPI) and whey protein hydrolysate (WPH) and calculated the surface hydrophobicities of WPI and WPH. MRPs were combined with WPI and WPH at a hydrolysis degree (DH) of 0.5% to form the complexes (DH = 0.0%) and (DH = 0.5%), respectively. Subsequently, the structural characteristics of complex (DH = 0.5%) and WPI were characterized and the color retention rates of both complexes and MRPs were investigated under different pretreatment conditions. The results showed that the maximum binding constant of WPI with MRPs was 0.670 ± 0.06 U and the maximum binding capacity was 180 U/g. Furthermore, the thermal degradation of complex (DH = 0.0%), complex (DH = 0.5%), and MRPs in a water bath at 50-100 °C followed a first-order kinetic model. Thus, the interaction of WPI with MRPs could alter the protein conformation of WPI and effectively protect the stability of MRPs.
PubMed: 37174284
DOI: 10.3390/foods12091745