Fatty Acid Biosynthesis Pathway Research Articles

Genetic insights of blood lipid metabolites on polycystic ovary syndrome risk: a bidirectional two-sample Mendelian randomization study.

Pathologically, metabolic disorder plays a crucial role in polycystic ovarian syndrome (PCOS). However, there is no conclusive evidence lipid metabolite levels to PCOS risk. In this study, genome-wide association study (GWAS) genetic data for 122 lipid metabolites were used to assign instrumental variables (IVs). PCOS GWAS were derived from a large-scale meta-analysis of 10,074 PCOS cases and 103,164 controls. An inverse variance weighted (IVW) analysis was the primary methodology used for Mendelian randomization (MR). For sensitivity analyses, Cochran Q test, MR-Egger intercept, MR-PRESSO, leave-one-out analysis,and Steiger test were performed. Furthermore, we conducted replication analysis, meta-analysis, and metabolic pathway analysis. Lastly, reverse MR analysis was used to determine whether the onset of PCOS affected lipid metabolites. This study detected the blood lipid metabolites and potential metabolic pathways that have a genetic association with PCOS onset. After IVW, sensitivity analyses, replication and meta-analysis, two pathogenic lipid metabolites of PCOS were finally identified: Hexadecanedioate (OR=1.85,95%CI=1.27-2.70, P=0.001) and Dihomo-linolenate (OR=2.45,95%CI=1.30-4.59, P=0.005). Besides, It was found that PCOS may be mediated by unsaturated fatty acid biosynthesis and primary bile acid biosynthesis metabolic pathways. Reverse MR analysis showed the causal association between PCOS and 2-tetradecenoyl carnitine at the genetic level (OR=1.025, 95% CI=1.003-1.048, P=0.026). Genetic evidence suggests a causal relationship between hexadecanedioate and dihomo-linolenate and the risk of PCOS. These compounds could potentially serve as metabolic biomarkers for screening PCOS and selecting drug targets. The identification of these metabolic pathways is valuable in guiding the exploration of the pathological mechanisms of PCOS, although further studies are necessary for confirmation.

Integrated serum metabolomics, 16S rRNA sequencing and bile acid profiling to reveal the potential mechanism of gentiopicroside against nonalcoholic steatohepatitis in lean mice

Ethnopharmacological relevanceLean nonalcoholic steatohepatitis (NASH) poses a serious threat to public health worldwide. Herbs of the genus Gentiana have been used for centuries to treat hepatic disease or have been consumed for hepatic protection efficiency. Gentiopicroside (GPS), the main bioactive component of Gentiana herbs, has been shown to be beneficial for protecting the liver, improving intestinal disorders, modulating bile acid profiles, ameliorating alcoholic hepatosteatosis, and so on. It is plausible to speculate that GPS may hold potential as a therapeutic strategy for lean NASH. However, no related studies have been conducted thus far. Aim of the studyThe present work aimed to investigate the benefit of GPS on NASH in a lean mouse model. Materials and methodsNASH in a lean mouse model was successfully established via a published method. GPS of 50 and 100 mg/kg were orally administered to verify the effect. Untargeted metabolomics, 16S rDNA sequencing and bile acid (BA) profiling, as well as qPCR and Western blotting analysis were employed to investigate the mechanism underlying the alleviating effect. ResultsGPS significantly reduced the increase in serum biochemicals and liver index, and attenuated the accumulation of fat in the livers of lean mice with NASH. Forty-two potential biomarkers were identified by metabolomics analysis, leading to abnormal metabolic pathways of primary bile acid biosynthesis and fatty acid biosynthesis, which were subsequently rebalanced by GPS. A decreased Firmicutes/Bacteroidetes (F/B) ratio and disturbed BA related GM profiles were revealed in lean mice with NASH but were partially recovered by GPS. Furthermore, serum profiling of 23 BAs confirmed that serum BA levels were elevated in the lean model but downregulated by GPS treatment. Pearson correlation analysis validated associations between BA profiles, serum biochemical indices and related GM. qPCR and Western blotting analysis further elucidated the regulation of genes associated with liver lipid synthesis and bile acid metabolism. ConclusionsGPS may ameliorate steatosis in lean mice with NASH, regulating the metabolomic profile, BA metabolism, fatty acid biosynthesis, and BA-related GM. All these factors may contribute to its beneficial effect.

Untargeted metabolomics study of mature human milk from women with and without gestational diabetes mellitus

Gestational diabetes mellitus (GDM) is a prevalent metabolic disorder during pregnancy that alters the metabolites in human milk. Integrated Gas Chromatography-Mass Spectrometry (GC–MS) and Liquid Chromatography-Mass Spectrometry (LC-MS) were employed for comprehensive identification and comparison of metabolites in mature human milk (MHM) from women with and without GDM. A total of 268 differentially expressed metabolites (DEMs) were identified. Among these, linoleic acid, arachidonic acid, 9R-HODE and L-glutamic acid were significantly elevated and 12,13-DHOME was significantly decreased in MHM of women with GDM. These metabolites are significantly enriched in linoleic acid metabolism, fatty acid biosynthesis, galactose metabolism and ABC transporters pathways. Disorders in these metabolic pathways are associated with insulin resistance and poor glucose metabolism indicating these conditions may persist postpartum.

Insight into interaction among soil microbial community, soil metabolomics and enzyme activity after long-term PAH stress

The problem of soil polycyclic aromatic hydrocarbon (PAH) pollution in coking plant sites has been widely studied in recent years, but there is a lack of research on the correlation between soil microorganisms, soil metabolomics, and soil properties. Thus, in this study, the long-term impact of coke combustion on soil microbial community structure, enzyme activities, and metabolic pathways within a former coking plant site was investigated. Soil samples were collected from both the coking production area (CA group) and office area (OLA group), approximately 0 to 20 cm in depth. Compared with OLA group, elevated levels of 16 PAHs in the list of USA EPA were detected by gas chromatography-mass spectrometry in the CA group. Several dominant microorganisms, such as Altererythrobacter, Lysobacter, and Sulfurifustis, were identified by 16 s ribosomal DNA sequencing in the CA group. The fatty acid biosynthesis pathway exhibited specific inhibition, while the phenylalanine metabolic pathway was promoted in response to PAH stress. Long-term PAH exposure led to the inhibition of soil urease activity. The co-occurrence network of microorganisms revealed intricate patterns of co-metabolism and co-adaptation within complex bacterial communities, facilitating their adaptation to and decomposition of soil-borne PAHs. This research could provide valuable insights into the community characteristics and metabolic mechanisms of microorganisms inhabiting PAH-polluted soil within coking plant sites. The findings enhance our understanding of the indigenous soil microbiome and its intricate network dynamics under the persistent stress of PAHs, contributing to a more comprehensive knowledge of soil ecosystems in such environments.

Ectoine maintains the flavor and nutritional quality of broccoli during postharvest storage

The bacterial derived osmolyte ectoine has been shown to stabilize cell structure and function, a property that may help to extend the shelf life of broccoli. The impact of ectoine on broccoli stored for 4 d at 20 °C and 90% relative humidity was investigated. Results indicated that 0.20% ectoine treatment maintained the quality of broccoli, by reducing rate of respiration and ethylene generation, while increasing the levels of total phenolics, flavonoids, TSS, soluble protein, and vitamin C, relative to control. Headspace-gas chromatography–mass spectrometry, transcriptomic and metabolomic analyses revealed that ectoine stabilized aroma components in broccoli by maintaining level of volatile compounds and altered the expression of genes and metabolites associated with sulfur metabolism, as well as fatty acid and amino acid biosynthesis pathways. These findings provide a greater insight into how ectoine preserves the flavor and nutritional quality of broccoli, thus, extending its shelf life.

The gapless genome assembly and multi-omics analyses unveil a pivotal regulatory mechanism of oil biosynthesis in the olive tree.

Olive is a valuable oil-bearing tree with fruits containing high levels of fatty acids. Oil production is a multifaceted process involving intricate interactions between fatty acid biosynthesis and other metabolic pathways that are affected by genetics and the developmental stages of the fruit. However, a comprehensive understanding of the underlying regulatory mechanisms is still lacking. Here, we generated a gap-free telomere-to-telomere assembly for Olea europaea cv. 'Leccino', representing an olive genome with the highest contiguity and completeness to date. The combination of time-course metabolomics and transcriptomics datasets revealed a negative correlation between fatty acid and flavonoid biosynthesis in the initial phase of olive fruit development, which was subject to an opposing regulatory mechanism mediated by the hub transcription factor MYC2. Multifaceted molecular assays demonstrated that MYC2 is a repressor of fatty acid biosynthesis by downregulating the expression of BCCP2 (biotin carboxylase carrier protein 2), while it acts as an activator of FLS (flavonol synthase), leading to an increase in flavonoid synthesis. Furthermore, the expression of MYC2 is regulated by fluctuations of methyl jasmonate content during olive fruit development. Our study completes a high-quality gapless genome of an olive cultivar, and provides new insight into the regulatory mechanisms underlying the biosynthesis of fatty acids and flavonoids in its fruit.

Transcriptome analyses of Acer Truncatum Bunge seeds to delineate the genes involved in fatty acid metabolism

BackgroundAcer truncatum Bunge is an economic, ecological, oil, and medicinal tree, and its kernel oil is rich in nervonic acid. It is crucial to explore the transcriptional expression patterns of genes affecting fatty acid synthesis to improve the quality of Acer truncatum oil.ResultsThis study used the seeds from high fatty acid strain YQC and those from low fatty acid strain Y38 as the test materials. Specifically, we performed a comparative transcriptome analysis of Y38 seeds and YQC to identify differentially expressed genes (DEGs) at two time points (seeds 30 days after the blooming period and 90 days after the blooming period). Compared with YQC_1 (YQC seeds at 30 days after the blooming period), a total of 3,618 DEGs were identified, including 2,333 up-regulated and 1,285 downregulated DEGs in Y38_1 (Y38 seeds at 30 days after blooming period). In the Y38_2 (Y38 seeds at 90 days after the blooming period) versus YQC_2 (YQC seeds at 90 days after the blooming period) comparison group, 9,340 genes were differentially expressed, including 5,422 up-regulated and 3,918 down-regulated genes. The number of DEGs in Y38 compared to YQC was significantly higher in the late stages of seed development. Gene functional enrichment analyses showed that the DEGs were mainly involved in the fatty acid biosynthesis pathway. And two fatty acid synthesis-related genes and seven nervonic acid synthesis-related genes were validated by qRT-PCR.ConclusionsThis study provides a basis for further research on biosynthesizing fatty acids and nervonic acidnervonic acids in A. truncatum seeds.

4-tert-Butylphenol impairs the liver by inducing excess liver lipid accumulation via disrupting the lipid metabolism pathway in zebrafish

Endocrine disrupting chemicals (EDCs) can disrupt normal endocrine function by interfering with the synthesis and release of hormones, causing adverse reactions to development, immunity, nerves, and reproduction. 4-tert-Butylphenol (4-t-BP) is disruptive to early zebrafish development, but its effects on zebrafish liver are unknown. In this study, the adverse effects of 4-t-BP on the liver were investigated using zebrafish as a model organism. 4-t-BP inhibited liver development in zebrafish embryos and induced liver damage in adult zebrafish. Even if F1 was not directly exposed to 4-t-BP, its growth and development were inhibited. 4-t-BP can lead to an increase in lipid accumulation, total cholesterol and triglycerides contents, and the activities of alanine transaminase and aspartate aminotransferase in zebrafish embryos and adult zebrafish livers, and also cause an acceleration of glucose metabolism in zebrafish embryos. In addition, qRT-PCR showed that 4-t-BP induced the changes in the expressions of liver development-, steroid and unsaturated fatty acid biosynthesis-, and glycerolipid and arachidonic acid metabolism-related genes in zebrafish embryos and inflammatory factors-, antioxidant enzymes- and lipid metabolism-related genes in adult zebrafish livers. Transcriptome sequencing of embryos showed that 4-t-BP altered the expressions of lipid metabolism pathways such as steroid and unsaturated fatty acid biosynthesis, glycerolipid, and arachidonic acid metabolism pathways. Therefore, 4-t-BP may be external stimuli that cause oxidative stress, inflammation, and lipid accumulation in zebrafish liver, resulting in tissue damage and dysfunction in zebrafish liver.

Molecular Regulatory Mechanisms Affecting Fruit Aroma.

Aroma, an important quality characteristic of plant fruits, is produced by volatile organic compounds (VOCs), mainly terpenes, aldehydes, alcohols, esters, ketones, and other secondary metabolites, in plant cells. There are significant differences in the VOC profile of various fruits. The main pathways involved in the synthesis of VOCs are the terpenoid, phenylalanine, and fatty acid biosynthesis pathways, which involve several key enzyme-encoding genes, transcription factors (TFs), and epigenetic factors. This paper reviews the main synthetic pathways of the main volatile components in fruit, summarizes studies on the regulation of aroma formation by key genes and TFs, summarizes the factors affecting the fruit aroma formation, describes relevant studies on the improvement of fruit flavor quality, and finally proposes potential challenges and prospects for future research directions. This study provides a theoretical basis for the further precise control of fruit aroma quality and variety improvement.

Preparation and InhA inhibitory properties of novel dehydroacetic acid-derived thiazoles

A series of 4-hydroxy-6-methyl-3-(1-(4-(aryl/methyl)thiazol-2-yl)-1H-pyrazol-3-yl)-2H-pyran-2-ones 3a–h have been synthesized from aryl/methyl halomethylketones and a key pyrazole intermediate 1 using a convenient one-pot synthesis method. All compounds were characterized by NMR and MS, and the structure of three of them (3a, 3b and 3f) was resolved by X-ray diffraction. These heteroatom-rich thiazole compounds were then evaluated as inhibitors of Mycobacterium tuberculosis InhA, a key enzyme involved in the type II fatty acid biosynthesis pathway of the mycobacterium. Although inhibitory activities were found to be rather weak, molecular docking studies were also been carried out to understand a possible mode of interaction with key residues in the enzyme’s active site.

Significance of Cellular Lipid Metabolism for the Replication of Rotaviruses and Other RNA Viruses.

The replication of species A rotaviruses (RVAs) involves the recruitment of and interaction with cellular organelles' lipid droplets (LDs), both physically and functionally. The inhibition of enzymes involved in the cellular fatty acid biosynthesis pathway or the inhibition of cellular lipases that degrade LDs was found to reduce the functions of 'viral factories' (viroplasms for rotaviruses or replication compartments of other RNA viruses) and decrease the production of infectious progeny viruses. While many other RNA viruses utilize cellular lipids for their replication, their detailed analysis is far beyond this review; only a few annotations are made relating to hepatitis C virus (HCV), enteroviruses, SARS-CoV-2, and HIV-1.

Upgrading soybean dreg to caproate via intermediate of lactate and mediator of biochar

To address the environmental hazards posed by high-yield soybean dreg (SD), a high-value strategy is firstly proposed by synthesizing caproate through chain elongation (CE). Optimized conditions for lactate-rich broth as intermediate, utilizing 50 % inoculum ratio, 40 g/L substrate concentration, and pH 5, resulting in 2.05 g/L caproate from direct fermentation. Leveraging lactate-rich broth supplemented with ethanol, caproate was optimized to 2.76 g/L under a refined electron donor to acceptor of 2:1. Furthermore, incorporating 20 g/L biochar elevated caproate production to 3.05 g/L and significantly shortened the lag phase. Mechanistic insights revealed that biochar’s surface-existed quinone and hydroquinone groups exhibit potent redox characteristics, thereby facilitating electron transfer. Moreover, biochar up-regulated the abundance of key genes involved in CE process (especially fatty acids biosynthesis pathway), also enriching Lysinibacillus and Pseudomonas as an unrecognized cooperation to CE. This study paves a way for sustainable development of SD by upgrading to caproate.

Enhanced medium-chain fatty acid production from sewage sludge by combined electro-fermentation and anaerobic fermentation

Electro-fermentation (EF) was combined with anaerobic fermentation (AF) to promote medium-chain fatty acid (MCFA) from sewage sludge. Results showed that EF at acidification process significantly increased short-chain fatty acid (SCFA) production of by 0.5 times (82.4 mmol C/L). AF facilitated the chain elongation (CE) process by enhancing the SCFA conversion. Combined EF at acidification and AF at CE (EF-AF) achieved the highest MCFA production of 27.9 mmol C/L, which was 20 %-866 % higher than the other groups. Electrochemical analyses showed that enhanced SCFA and MCFA production was accompanied with good electrochemical performance at acidification and CE. Microbial analyses showed that EF-AF promoted MCFA production by enriching electrochemically active bacteria (EAB, Bacillus sp.). Enzyme analyses indicated that EF-AF promoted MCFA production by enriching the functional enzymes involved in Acetyl-CoA formation and the fatty acid biosynthesis (FAB) pathway. This study provided new insights into the production of MCFA from enhanced sewage sludge.

Proteomics and metabolic burden analysis to understand the impact of recombinant protein production in E. coli

The impact of recombinant protein production (RPP) on host cells and the metabolic burden associated with it undermine the efficiency of the production system. This study utilized proteomics to investigate the dynamics of parent and recombinant cells induced at different time points for RPP. The results revealed significant changes in both transcriptional and translational machinery that may have impacted the metabolic burden, growth rate of the culture and the RPP. The timing of protein synthesis induction also played a critical role in the fate of the recombinant protein within the host cell, affecting protein and product yield. The study identified significant differences in the expression of proteins involved in fatty acid and lipid biosynthesis pathways between two E. coli host strains (M15 and DH5⍺), with the E. coli M15 strain demonstrating superior expression characteristics for the recombinant protein. Overall, these findings contribute to the knowledge base for rational strain engineering for optimized recombinant protein production.

Integrated Metabolomic and Transcriptomic Analysis Reveals the Underlying Antibacterial Mechanisms of the Phytonutrient Quercetin-Induced Fatty Acids Alteration in Staphylococcus aureus ATCC 27217.

The utilization of natural products in food preservation represents a promising strategy for the dual benefits of controlling foodborne pathogens and enhancing the nutritional properties of foods. Among the phytonutrients, flavonoids have been shown to exert antibacterial effects by disrupting bacterial cell membrane functionality; however, the underlying molecular mechanisms remain elusive. In this study, we investigated the effect of quercetin on the cell membrane permeability of Staphylococcus aureus ATCC 27217. A combined metabolomic and transcriptomic approach was adopted to examine the regulatory mechanism of quercetin with respect to the fatty acid composition and associated genes. Kinetic analysis and molecular docking simulations were conducted to assess quercetin's inhibition of β-ketoacyl-acyl carrier protein reductase (FabG), a potential target in the bacterial fatty acid biosynthesis pathway. Metabolomic and transcriptomic results showed that quercetin increased the ratio of unsaturated to saturated fatty acids and the levels of membrane phospholipids. The bacteria reacted to quercetin-induced stress by attempting to enhance fatty acid biosynthesis; however, quercetin directly inhibited FabG activity, thereby disrupting bacterial fatty acid biosynthesis. These findings provide new insights into the mechanism of quercetin's effects on bacterial cell membranes and suggest potential applications for quercetin in bacterial inhibition.

Metabolomics revealed that toxic cyanobacteria stress reduced the flavor quality of Bellamya aeruginosa

The environmental impact of increased eutrophication and frequent cyanobacterial blooms on the growth and reproduction of aquatic organisms has become increasingly prominent in recent years. Bellamya aeruginosa is a nutrient-rich aquatic snail consumed by humans, and environmental changes may decrease its meat quality. However, the specific characteristics of muscle metabolism and flavor quality in freshwater snails and their response patterns to bloom-forming cyanobacterial stress have not been reported. Therefore, in this study, alterations in metabolites in the snail muscle after following feeding on toxic Microcystis aeruginosa were investigated using untargeted metabolomics. A total of 1,128 metabolites were identified, and the metabolic pathways of unsaturated fatty acid biosynthesis and purine, glutathione, and glycerophospholipid metabolism in snails fed toxic cyanobacteria differed from those in snails fed Chlorella vulgaris. Quantitative analysis showed increased levels of bitter-free amino acids, such as tyrosine, phenylalanine, and histidine, after consuming toxic cyanobacteria for 42 d, whereas a relative decrease was observed in the levels of umami- and sweet-free amino acids, such as glutamic acid, aspartic acid, serine, threonine, and glicine. The muscles of snails fed toxic cyanobacteria exhibited higher hypoxanthine and hypoxanthine nucleoside and lower adenosine triphosphate, adenine nucleotide, adenine nucleoside diphosphate, and hypoxanthine nucleotide contents than those of snails fed C. vulgaris. Furthermore, increased metabolites, such as stearic acid, palmitic acid, and cytidine diphosphate choline, and decreased metabolites, such as docosapentaenoic acid, docosahexaenoic acid, adrenoic acid, and L-glutamic acid, reflect the harmful effects of toxic cyanobacteria on the nutritional value and flesh quality of B. aeruginosa. This study comprehensively evaluated the effects of cyanobacterial blooms on freshwater gastropods, providing an important theoretical basis for the quality, safety, and sustainable development of snails as food and related processing industries.

Delivery of miRNAs Using Porous Silicon Nanoparticles Incorporated into 3D Hydrogels Enhances MSC Osteogenesis by Modulation of Fatty Acid Signaling and Silicon Degradation.

Strategies incorporating mesenchymal stromal cells (MSC), hydrogels and osteoinductive signals offer promise for bone repair. Osteoinductive signals such as growth factors face challenges in clinical translation due to their high cost, low stability and immunogenicity leading to interest in microRNAs as a simple, inexpensive and powerful alternative. The selection of appropriate miRNA candidates and their efficient delivery must be optimised to make this a reality. This study evaluated pro-osteogenic miRNAs and used porous silicon nanoparticles modified with polyamidoamine dendrimers (PAMAM-pSiNP) to deliver these to MSC encapsulated within gelatin-PEG hydrogels. miR-29b-3p, miR-101-3p and miR-125b-5p are strongly pro-osteogenic and are shown to target FASN and ELOVL4 in the fatty acid biosynthesis pathway to modulate MSC osteogenesis. Hydrogel delivery of miRNA:PAMAM-pSiNP complexes enhanced transfection compared to 2D. The osteogenic potential of hBMSC in hydrogels with miR125b:PAMAM-pSiNP complexes is evaluated. Importantly, a dual-effect on osteogenesis occurred, with miRNAs increasing expression of alkaline phosphatase (ALP) and Runt-related transcription factor 2 (RUNX2) whilst the pSiNPs enhanced mineralisation, likely via degradation into silicic acid. Overall, this work presents insights into the role of miRNAs and fatty acid signalling in osteogenesis, providing future targets to improve bone formation and a promising system to enhance bone tissue engineering.

Reactive oxygen species derived from NADPH oxidase as signaling molecules regulate fatty acids and astaxanthin accumulation in Chromochloris zofingiensis.

Abiotic stresses can increase the total fatty acid (TFA) and astaxanthin accumulation in microalgae. However, it remains unknown whether a unified signal transduction mechanism exists under different stresses. This study explored the link between nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-derived reactive oxygen species (ROS) and the accumulation of fatty acids and astaxanthin in Chromochloris zofingiensis under three abiotic stresses. Results showed significant increases in fatty acid, astaxanthin, and ROS levels under nitrogen deficiency, phosphorus deficiency, and high-salinity stress. The introduction of the NADPH oxidase inhibitor diphenyleneiodonium (DPI) decreased the content of these components. This underscores the pivotal role of NADPH oxidase-derived ROS in the accumulation of fatty acid and astaxanthin under abiotic stress. Analysis of transcriptomes across three conditions following DPI addition revealed 1,445 shared differentially expressed genes (DEGs). Enrichment analysis revealed that biotin, betalain, thiamine, and glucosinolate may be important in stress responses. The heatmap demonstrated that DPI notably suppressed gene expression in the fatty acid and carotenoid biosynthesis pathways. Our findings underscore the pivotal role of NADPH oxidase-derived ROS in the accumulation of fatty acid and astaxanthin under abiotic stresses.

An upstream signaling gene calmodulin regulates the synthesis of insect wax via activating fatty acid biosynthesis pathway

Insect wax accumulates on the surface of insect cuticle, which acts as an important protective barrier against rain, ultraviolet light radiation, pathogens, etc. The waxing behavior, wax composition and molecular mechanism underling wax biosynthesis are unclear in dustywings. Herein, the current study determined the vital developmental stage for waxing behavior in dustywings, examined the components of waxy secretions, and identified key regulatory genes for wax biosynthesis. The wax glands were mainly located on the thorax and abdomen of dustywing adults. The adults spread the waxy secretions over their entire body surface. The metabolomics analysis identified 32 lipids and lipid-like molecules, 15 organic acids and derivatives, 7 benzenoids, etc. as the main components of waxy secretions. The fatty acids represented the largest proportion of the category of lipid and lipid-like molecules. The conjoint analysis of metabolomics and transcriptomics identified two crucial genes fatty acyl-CoA reductase (CsFAR) and calmodulin (CsCaM) for wax biosynthesis. The down-regulation of these genes via nanocarrier-mediated RNA interference technology significantly reduced the amount of wax particles. Notably, the RNAi of CsCaM apparently suppressed the expression of most genes in fatty acid biosynthesis pathway, indicating the CsCaM might act as a main upstream regulator of fatty acid biosynthesis pathway.

Dissecting Holistic Metabolic Acclimatization of Mucor circinelloides WJ11 Defective in Carotenoid Biosynthesis.

Mucor circinelloides WJ11 is a lipid-producing strain with industrial potential. A holistic approach using gene manipulation and bioprocessing development has improved lipid production and the strain's economic viability. However, the systematic regulation of lipid accumulation and carotenoid biosynthesis in M. circinelloides remains unknown. To dissect the metabolic mechanism underlying lipid and carotenoid biosynthesis, transcriptome analysis and reporter metabolites identification were implemented between the wild-type (WJ11) and ΔcarRP WJ11 strains of M. circinelloides. As a result, transcriptome analysis revealed 10,287 expressed genes, with 657 differentially expressed genes (DEGs) primarily involved in amino acid, carbohydrate, and energy metabolism. Integration with a genome-scale metabolic model (GSMM) identified reporter metabolites in the ΔcarRP WJ11 strain, highlighting metabolic pathways crucial for amino acid, energy, and nitrogen metabolism. Notably, the downregulation of genes associated with carotenoid biosynthesis and acetyl-CoA generation suggests a coordinated relationship between the carotenoid and fatty acid biosynthesis pathways. Despite disruptions in the carotenoid pathway, lipid production remains stagnant due to reduced acetyl-CoA availability, emphasizing the intricate metabolic interplay. These findings provide insights into the coordinated relationship between carotenoid and fatty acid biosynthesis in M. circinelloides that are valuable in applied research to design optimized strains for producing desired bioproducts through emerging technology.