-
MSystems Oct 2021Nitrogen in different chemical forms is critical for metabolic alterations in strains and associated pigment diversity. In this study, we observed that ammonium-form...
Nitrogen in different chemical forms is critical for metabolic alterations in strains and associated pigment diversity. In this study, we observed that ammonium-form nitrogen was superior in promoting the biosynthesis of pigments (MPs) when compared with nitrate and organic forms. Moreover, with any nitrogen source, the production of yellow and orange pigments was highly synchronized but distantly related to red pigments. However, transcriptional analyses of MP gene clusters suggested a low contribution to MP accumulation, suggesting that MP-limiting factors were located outside the gene cluster. Our metabolomic analyses demonstrated that red pigment biosynthesis was closely related to intracellular amino acids, whereas orange and yellow pigments were associated with nucleotides. In addition, weighted gene coexpression network analyses (WGCNA) based on transcriptomic data showed that multiple primary metabolic pathways were closely related to red pigment production, while several secondary pathways were related to orange pigments, and others were involved with yellow pigment regulation. These findings demonstrate that pigment diversity in is under combined regulation at metabolomic and transcriptomic levels. Natural MPs containing a mixture of red, orange, and yellow pigments are widely used as food coloring agents. MP diversity provides foods with versatile colors and health benefits but, in turn, complicate efforts to achieve maximum yield or desirable combination of pigments during the manufacturing process. Apart from the MP biosynthetic gene cluster, interactions between the main biosynthetic pathways and other intracellular genes/metabolites are critical to our understanding of MP differentiation. The integrative multiomics analytical strategy provides a technical platform and new perspectives for the identification of metabolic shunting mechanisms in MP biosynthesis. Equally, our research highlights the influence of intracellular metabolic alterations on MP differentiation, which will facilitate the rational engineering and optimization of MP production in the future.
PubMed: 34491088
DOI: 10.1128/mSystems.00807-21 -
Food & Function Jul 2014Edible fungi of the Monascus species have been used as traditional Chinese medicine in eastern Asia for several centuries. Monascus-fermented products possess a number... (Review)
Review
Edible fungi of the Monascus species have been used as traditional Chinese medicine in eastern Asia for several centuries. Monascus-fermented products possess a number of functional secondary metabolites, including the anti-inflammatory pigments monascin and ankaflavin. Monascin has been shown to prevent or ameliorate several conditions, including hypercholesterolemia, hyperlipidemia, diabetes, and obesity. Recently, monascin has been shown to improve hyperglycemia, attenuate oxidative stress, inhibit insulin resistance, and suppress inflammatory cytokine production. In our recent study, we have found that monascin is a peroxisome proliferator-activated receptor-gamma (PPARgamma) agonist. The PPARgamma agonist activity had been investigated and its exerted benefits are inhibition of inflammation in methylglyoxal (MG)-treated rats, prevention of pancreas impairment causing advanced glycation endproducts (AGEs), promotion of insulin expression in vivo and in vitro, and attenuated carboxymethyllysine (CML)-induced hepatic stellate cell (HSC) activation in the past several years. Moreover, our studies also demonstrated that monascin also activated nuclear factor-erythroid 2-related factor 2 (Nrf2) in pancreatic RIN-m5F cell line thereby invading methylglyoxal induced pancreas dysfunction. In this review, we focus on the chemo-preventive properties of monascin against metabolic syndrome through PPARgamma and Nrf2 pathways.
Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Diabetes Mellitus; Flavins; Glycation End Products, Advanced; Heterocyclic Compounds, 3-Ring; Humans; Hypoglycemic Agents; Insulin; Liver; Monascus; NF-E2-Related Factor 2; PPAR gamma; Pancreas; Rats
PubMed: 24752777
DOI: 10.1039/c3fo60575b -
Frontiers in Microbiology 2021Cocultivation is an emerging and potential way to investigate microbial interaction in the laboratory. Extensive researches has been carried out over the years, but some...
Cocultivation is an emerging and potential way to investigate microbial interaction in the laboratory. Extensive researches has been carried out over the years, but some microorganism cocultivation are not easy to implement in the laboratory, especially the fungus-fungus (FF) cocultivation, owing to the obstacles such as fungal different growth rate, limited growing space, hyphae intertwining, and difficulty of sample separation, etc. In this research, a double-sided petri dish (DSPD) was designed and carried out as a tool to study FF cocultivation in the laboratory. A natural FF cocultivation of spp. and inspired from black-skin-red-koji (BSRK), were studied. By using DSPD, the aforementioned obstacles in the FF cocultivation study were overcome through co-culturing spp. and on each side of DSPD. The characteristics of monocultured and co-cultured spp. and were compared and analyzed, including colonial and microscopic morphologies, and main secondary metabolites (SMs) of spp. analyzed by high performance liquid chromatography. And a novel SM was found to be produced by M7 when co-cultured with CBS 513.88. Since the above mentioned obstacles, were overcome, we obtained good quality of transcriptome data for further analysis. These results indicate that DSPD might be an efficient tool for investigation of microbial interaction, in particular, for FF interaction.
PubMed: 34177849
DOI: 10.3389/fmicb.2021.670684 -
Frontiers in Microbiology 2023Species of the genus are economically important and widely used in the production of food colorants and monacolin K. However, they have also been known to produce the...
BACKGROUND
Species of the genus are economically important and widely used in the production of food colorants and monacolin K. However, they have also been known to produce the mycotoxin citrinin. Currently, taxonomic knowledge of this species at the genome level is insufficient.
METHODS
This study presents genomic similarity analyses through the analysis of the average nucleic acid identity of the genomic sequence and the whole genome alignment. Subsequently, the study constructed a pangenome of by reannotating all the genomes and identifying a total of 9,539 orthologous gene families. Two phylogenetic trees were constructed based on 4,589 single copy orthologous protein sequences and all the 5,565 orthologous proteins, respectively. In addition, carbohydrate active enzymes, secretome, allergic proteins, as well as secondary metabolite gene clusters were compared among the included 15 strains.
RESULTS
The results clearly revealed a high homology between and , and their distant relationship with . Accordingly, all the included 15 strains should be classified into two distinctly evolutionary clades, namely the clade and the - clade. Moreover, gene ontology enrichment showed that the - clade had more orthologous genes involved with environmental adaptation than the clade. Compared to , all the species had a substantial gene loss of carbohydrate active enzymes. Potential allergenic and fungal virulence factor proteins were also found in the secretome of . Furthermore, this study identified the pigment synthesis gene clusters present in all included genomes, but with multiple nonessential genes inserted in the gene cluster of and compared to . The citrinin gene cluster was found to be intact and highly conserved only among genomes. The monacolin K gene cluster was found only in the genomes of and , but the sequence was more conserved in
CONCLUSION
This study provides a paradigm for phylogenetic analysis of the genus , and it is believed that this report will lead to a better understanding of these food microorganisms in terms of classification, metabolic differentiation, and safety.
PubMed: 37303795
DOI: 10.3389/fmicb.2023.1199144 -
Food Chemistry May 2022The aim of this study was to investigate the digestion and fermentation properties of fish protein fermented by Monascus. Semi-dried fish was fermented by applying...
The aim of this study was to investigate the digestion and fermentation properties of fish protein fermented by Monascus. Semi-dried fish was fermented by applying Monascus purpureus Went M 3.439. Our results show that the Monascus fermentation of the fish protein enriched the free amino acids and achieved a relatively higher glutamate content than the control group. The Monascus treatment promoted the decomposition of the fish protein during in vitro digestion, reduced the ammonia and indole content and tended to increase the propionic acid content during in vitro fermentation. The Monascus treatment considerably changed the gut microbiota composition, and particularly increased the relative abundance of Parabacteroides in the in vitro fermentation model of human distal colon. Consumption of Monascus fermented fish protein could result in positive changes in fermentation metabolites and gut microbiota, which brings potential health benefits.
Topics: Animals; Digestion; Fermentation; Fish Proteins; Gastrointestinal Microbiome; Humans; Monascus
PubMed: 34999460
DOI: 10.1016/j.foodchem.2021.132000 -
Molecules (Basel, Switzerland) Mar 2017The effect of light on and the underlying mechanism have received a great deal of interest for the industrial application of pigments. In this study, we have examined...
The effect of light on and the underlying mechanism have received a great deal of interest for the industrial application of pigments. In this study, we have examined the effects of blue light on the culture morphology, mycelium growth, pigments, and citrinin yield of in liquid-state and oscillation fermentation, and explored the mechanism at a physiological level. It was found that blue light affected the colony morphology, the composition (chitin content), and permeability of the mycelium cell wall in static liquid culture, which indicates blue light benefits pigments secreting from aerial mycelium to culture medium. In liquid oscillation fermentation, the yields of pigments in fermentation broth (darkness 1741 U/g, blue light 2206 U/g) and mycelium (darkness 2442 U/g, blue light 1900 U/g) cultured under blue light and darkness are different. The total pigments produced per gram of mycelium under blue light was also higher (4663 U/g) than that in darkness (4352 U/g). However, the production of citrinin (88 μg/g) under blue light was evidently lower than that in darkness (150 μg/g). According to the degradation of citrinin caused by blue light and hydrogen peroxide, it can be concluded that blue light could degrade citrinin and inhibit the catalase activity of mycelium, subsequently suppressing the decomposition of hydrogen peroxide, which is the active species that degrades citrinin.
Topics: Chromatography, High Pressure Liquid; Citrinin; Culture Media; Fermentation; Glucosamine; Hydrogen Peroxide; Light; Monascus; Mycelium; Phenotype; Pigments, Biological
PubMed: 28257052
DOI: 10.3390/molecules22030385 -
MBio Feb 2020Despite the important biological activities of natural product naphthoquinones, the biosynthetic pathways of and resistance mechanisms against such compounds remain...
Despite the important biological activities of natural product naphthoquinones, the biosynthetic pathways of and resistance mechanisms against such compounds remain poorly understood in fungi. Here, we report that the genes responsible for the biosynthesis of naphthoquinones (monasones) reside within the gene cluster for azaphilone pigments (MonAzPs). We elucidate the biosynthetic pathway of monasones by a combination of comparative genome analysis, gene knockouts, heterologous coexpression, and and enzymatic reactions to show that this pathway branches from the first polyketide intermediate of MonAzPs. Furthermore, we propose that the monasone subset of biosynthetic genes also encodes a two-tiered resistance strategy in which an inducible monasone-specific exporter expels monasones from the mycelia, while residual intracellular monasones may be rendered nontoxic through a multistep reduction cascade. The genes for naphthoquinone (monasone) biosynthesis are embedded in and form a composite supercluster with the azaphilone pigment biosynthetic gene cluster. Early biosynthetic intermediates are shared by the two pathways. Some enzymes encoded by the supercluster play double duty in contributing to both pathways, while others are specific for one or the other pathway. The monasone subcluster is independently regulated and inducible by elicitation with competing microorganisms. This study illustrates genomic and biosynthetic parsimony in fungi and proposes a potential path for the evolution of the mosaic-like azaphilone-naphthoquinone supercluster. The monasone subcluster also encodes a two-tiered self-resistance mechanism that models resistance determinants that may transfer to target microorganisms or emerge in cancer cells in case of naphthoquinone-type cytotoxic agents.
Topics: Biosynthetic Pathways; Drug Resistance, Fungal; Monascus; Multigene Family; Naphthoquinones
PubMed: 32019788
DOI: 10.1128/mBio.02676-19 -
Frontiers in Pharmacology 2020Hyperlipidemia can easily cause atherosclerosis and induce cardiovascular and cerebrovascular diseases. Red yeast rice (RYR) contains a variety of active ingredients and...
Hyperlipidemia can easily cause atherosclerosis and induce cardiovascular and cerebrovascular diseases. Red yeast rice (RYR) contains a variety of active ingredients and is commonly used as medicine and food, and has pharmacological effects such as lowering blood lipids. In this study, we select Monascus strain SHM1105 with a high yield of Monacolin K and monascus pigment (PIG), and studied the effects of the RYR and PIG fermented by this strain on blood lipids, intestinal flora, and liver transcriptome in hyperlipidemia model rats. The experimental results show that, compared with the high-fat model group, the weight growth rate, liver weight ratio, kidney weight ratio, spleen weight ratio, and fat weight ratio of rats in the gavage lovastatin (LOV), RYR, and PIG group were all significantly decreased ( < 0.05). Intervention with RYR and PIG can significantly reduce the serum TC, TG, and LDL-C levels, which has the effect of lowering blood lipids. The 16SrDNA sequencing results showed that the ratio of Firmicutes/Bacteroidetes decreased significantly ( ≤ 0.01) after the intervention of LOV, RYR, and PIG; the abundance of the ratio of , , , and also changed. The combined analysis of transcriptome and metabolome showed that lovastatin, RYR, and PIG can all improve lipid metabolism in rats by regulating Steroid hormone biosynthesis, Glycerolipid metabolism, and the Arachidonic acid metabolism pathway. In addition, RYR and PIG also have a unique way of regulating blood lipids. Although a lot of research on the lipid-lowering components of Monascus rice and the single pigment component of Monascus has been carried out, the actual application is RYR and pigments as mixtures, as a mixture of RYR and PIG contains a variety of biologically active ingredients, and each component may have a synergistic effect. Hence it has a lipid-lowering mechanism that lovastatin does not have. Therefore, RYR and PIG are effective in reducing lipid potential development and can be utilized in functional foods.
PubMed: 33551805
DOI: 10.3389/fphar.2020.599760 -
Frontiers in Microbiology 2022spp. are traditional medicinal and edible filamentous fungi in China, and can produce various secondary metabolites, such as pigments (MPs) and citrinin (CIT). Genetic...
spp. are traditional medicinal and edible filamentous fungi in China, and can produce various secondary metabolites, such as pigments (MPs) and citrinin (CIT). Genetic modification methods, such as gene knock-out, complementation, and overexpression, have been used extensively to investigate the function of related genes in spp.. However, the resistance selection genes that can have been used for genetic modification in spp. are limited, and the gene replacement frequency (GRF) is usually <5%. Therefore, we are committed to construct a highly efficient gene editing system without resistance selection marker gene. In this study, using M7 as the starting strain, we successfully constructed a so-called markerlessly and highly genetic modification system including the mutants ΔΔ and ΔΔ::, in which we used the endogenous gene from M7 instead of the resistance marker gene as the screening marker, and simultaneously deleted related to non-homologous end joining in M7. Then, the morphology, the growth rate, the production of MPs and CIT of the mutants were analyzed. And the results show that the mutant strains have normal mycelia, cleistothecia and conidia on PDA+Uridine(U) plate, the biomass of each mutant is also no different from M7. However, the U addition also has a certain effect on the orange and red pigments yield of M7, which needs our further study. Finally, we applied the system to delete multiple genes from M7 separately or continuously without any resistance marker gene, and found that the average GRF of ΔΔ was about 18 times of that of M7. The markerlessly and highly genetic modification system constructed in current study not only will be used for multi-gene simultaneous modification in spp., and also lays a foundation for investigating the effects of multi-genes modification on spp..
PubMed: 35979480
DOI: 10.3389/fmicb.2022.952323 -
Yeast (Chichester, England) Jan 2023When Monascus purpureus was co-cultured with Saccharomyces cerevisiae, we noted significant changes in the secondary metabolism and morphological development of...
When Monascus purpureus was co-cultured with Saccharomyces cerevisiae, we noted significant changes in the secondary metabolism and morphological development of Monascus. In yeast co-culture, although the pH was not different from that of a control, the Monascus mycelial biomass increased during fermentation, and the Monacolin K yield was significantly enhanced (up to 58.87% higher). However, pigment production did not increase. Co-culture with S. cerevisiae significantly increased the expression levels of genes related to Monacolin K production (mokA-mokI), especially mokE, mokF, and mokG. Linoleic acid, that has been implicated in playing a regulating role in the secondary metabolism and morphology of Monascus, was hypothesized to be the effector. Linoleic acid was detected in the co-culture, and its levels changed during fermentation. Addition of linoleic acid increased Monacolin K production and caused similar morphological changes in Monascus spores and mycelia. Exogenous linoleic acid also significantly upregulated the transcription levels of all nine genes involved in the biosynthesis of Monacolin K (up to 69.50% higher), consistent with the enhanced Monacolin K yield. Taken together, our results showed the effect of S. cerevisiae co-culture on M. purpureus and suggested linoleic acid as a specific quorum-sensing molecule in Saccharomyces-Monascus co-culture.
Topics: Linoleic Acid; Monascus; Saccharomyces cerevisiae; Coculture Techniques; Fermentation; Lovastatin
PubMed: 36514193
DOI: 10.1002/yea.3831