Microbial polyphenol metabolism is part of the thawing permafrost carbon cycle.

With rising global temperatures, permafrost carbon stores are vulnerable to microbial degradation. The enzyme latch theory states that polyphenols should accumulate in saturated peatlands due to diminished phenol oxidase activity, inhibiting resident microbes and promoting carbon stabilization. Pairing microbiome and geochemical measurements along a permafrost thaw-induced saturation gradient in Stordalen Mire, a model Arctic peatland, we confirmed a negative relationship between phenol oxidase expression and saturation but failed to support other trends predicted by the enzyme latch. To inventory alternative polyphenol removal strategies, we built CAMPER, a gene annotation tool leveraging polyphenol enzyme knowledge gleaned across microbial ecosystems. Applying CAMPER to genome-resolved metatranscriptomes, we identified genes for diverse polyphenol-active enzymes expressed by various microbial lineages under a range of redox conditions. This shifts the paradigm that polyphenols stabilize carbon in saturated soils and highlights the need to consider both oxic and anoxic polyphenol metabolisms to understand carbon cycling in changing ecosystems.

Vertical differences in carbon metabolic diversity and dominant flora of soil bacterial communities in farmlands.

The carbon cycle in soil is significantly influenced by soil microbes. To investigate the vertical distribution of the dominant groups in agricultural soil and the carbon metabolic diversity of soil bacteria, 45 soil samples from the 0 ~ 50 cm soil layer in Hunan tobacco-rice multiple cropping farmland were collected in November 2017, and the carbon diversity of the soil bacterial community, bacterial community composition and soil physical and chemical properties were determined. The results showed that the carbon metabolic capabilities and functional diversity of the soil bacterial community decreased with depth. The three most widely used carbon sources for soil bacteria were carbohydrates, amino acids, and polymers. The dominant bacterial groups in surface soil (such as Chloroflexi, Acidobacteriota, and Bacteroidota) were significantly positively correlated with the carbon metabolism intensity. The alkali-hydrolysable nitrogen content, soil bulk density and carbon-nitrogen ratio were the key soil factors driving the differences in carbon metabolism of the soil bacterial communities in the different soil layers.

Dearomatization drives complexity generation in freshwater organic matter.

Dissolved organic matter (DOM) is one of the most complex, dynamic and abundant sources of organic carbon, but its chemical reactivity remains uncertain1-3. Greater insights into DOM structural features could facilitate understanding its synthesis, turnover and processing in the global carbon cycle4,5. Here we use complementary multiplicity-edited 13C nuclear magnetic resonance (NMR) spectra to quantify key substructures assembling the carbon skeletons of DOM from four main Amazon rivers and two mid-size Swedish boreal lakes. We find that one type of reaction mechanism, oxidative dearomatization (ODA), widely used in organic synthetic chemistry to create natural product scaffolds6-10, is probably a key driver for generating structural diversity during processing of DOM that are rich in suitable polyphenolic precursor molecules. Our data suggest a high abundance of tetrahedral quaternary carbons bound to one oxygen and three carbon atoms (OCqC3 units). These units are rare in common biomolecules but could be readily produced by ODA of lignin-derived and tannin-derived polyphenols. Tautomerization of (poly)phenols by ODA creates non-planar cyclohexadienones, which are subject to immediate and parallel cycloadditions. This combination leads to a proliferation of structural diversity of DOM compounds from early stages of DOM processing, with an increase in oxygenated aliphatic structures. Overall, we propose that ODA is a key reaction mechanism for complexity acceleration in the processing of DOM molecules, creation of new oxygenated aliphatic molecules and that it could be prevalent in nature.

Uneven response of phytoplankton-bacteria coupling under Saharan dust pulse and ultraviolet radiation in the south-western Mediterranean Sea.

The microbial carbon (C) flux in the ocean is a key functional process governed by the excretion of organic carbon by phytoplankton (EOC) and heterotrophic bacterial carbon demand (BCD). Ultraviolet radiation (UVR) levels in upper mixed layers and increasing atmospheric dust deposition from arid regions may alter the degree of coupling in the phytoplankton-bacteria relationship (measured as BCD:EOC ratio) with consequences for the C-flux through these compartments in marine oligotrophic ecosystem. Firstly, we performed a field study across the south-western (SW) Mediterranean Sea to assess the degree of coupling (BCD:EOC) and how it may be related to metabolic balance (total primary production: community respiration; PPT:CR). Secondly, we conducted a microcosm experiment in two contrasting areas (heterotrophic nearshore and autotrophic open sea) to test the impact of UVR and dust interaction on microbial C flux. In the field study, we found that BCD was not satisfied by EOC (i.e., BCD:EOC >1; uncoupled phytoplankton-bacteria relationship). BCD:EOC ratio was negatively related to PPT:CR ratio across the SW Mediterranean Sea. A spatial pattern emerged, i.e. in autotrophic open sea stations uncoupling was less severe (BCD:EOC ranged 1-2), whereas heterotrophic nearshore stations uncoupling was more severe (BCD:EOC > 2). In the experimental study, in the seawater both enriched with dust and under UVR, BCD:EOC ratio decreased by stimulating autotrophic processes (particulate primary production (PPP) and EOC) in the heterotrophic nearshore area, whereas BCD:EOC increased by stimulating heterotrophic processes [heterotrophic bacterial production (HBP), bacterial growth efficiency (BGE), bacterial respiration (BR)] in the autotrophic open sea. Our results show that this spatial pattern could be reversed under future UVR × Dust scenario. Overall, the impact of greater dust deposition and higher UVR levels will alter the phytoplankton-bacteria C-flux with consequences for the productivity of both communities, their standing stocks, and ultimately, the ecosystem's metabolic balance at the sea surface.

The dual roles of dissimilatory iron reduction in the carbon cycle: The "iron mesh" effect can increase inorganic carbon sequestration.

Dissimilatory iron reduction (DIR) can drive the release of organic carbon (OC) as carbon dioxide (CO2 ) by mediating electron transfer between organic compounds and microbes. However, DIR is also crucial for carbon sequestration, which can affect inorganic-carbon redistribution via iron abiotic-phase transformation. The formation conditions of modern carbonate-bearing iron minerals (ICFe ) and their potential as a CO2 sink are still unclear. A natural environment with modern ICFe , such as karst lake sediment, could be a good analog to explore the regulation of microbial iron reduction and sequential mineral formation. We find that high porosity is conducive to electron transport and dissimilatory iron-reducing bacteria activity, which can increase the iron reduction rate. The iron-rich environment with high calcium and OC can form a large sediment pore structure to support rapid DIR, which is conducive to the formation and growth of ICFe . Our results further demonstrate that the minimum DIR threshold suitable for ICFe formation is 6.65 µmol g-1 dw day-1 . DIR is the dominant pathway (average 66.93%) of organic anaerobic mineralization, and the abiotic-phase transformation of Fe2+ reduces CO2 emissions by ~41.79%. Our findings indicate that as part of the carbon cycle, DIR not only drives mineralization reactions but also traps carbon, increasing the stability of carbon sinks. Considering the wide geographic distribution of DIR and ICFe , our findings suggest that the "iron mesh" effect may become an increasingly important vector of carbon sequestration.

Nuclear mutagenesis and adaptive evolution improved photoautotrophic growth of Euglena gracilis with flue-gas CO2 fixation.

To effectively improve biomass growth and flue-gas CO2 fixation of microalgae, acid-tolerant Euglena gracilis was modified with cobalt-60 γ-ray irradiation and polyethylene glycol (PEG) adaptive screening to obtain the mutant strain M800. The biomass dry weight and maximum CO2 fixation rate of M800 were both 1.47 times higher than that of wild strain, which was attributed to a substantial increase in key carbon fixation enzyme RuBisCO activity and photosynthetic pigment content. The high charge separation quantum efficiency in PSII reaction center, efficient light utilization and energy regulation that favors light conversion, were the underlying drivers of efficient photosynthetic carbon fixation in M800. M800 had stronger antioxidant capacity in sufficient high-carbon environment, alleviating lipid peroxidation damage. After adding 1 mM PEG, biomass dry weight of M800 reached 2.31 g/L, which was 79.1 % higher than that of wild strain. Cell proliferation of M800 was promoted, the apoptosis and necrosis rates decreased.

Taxonomic study and diversity of Postia s.lat. in Swat, Pakistan: addition of five brown rot Polypores to the country.

Brown rot Polypores are ecologically significant as they play a crucial role in maintaining the carbon cycle and contribute to humus formation in forest ecosystems through their lignocellulose degradation ability. It is important to note that some species can significantly impact timber, potentially causing decay in economically valuable wood. Many Asian countries including Pakistan are still under the exploratory phase and have undocumented species diversity in Polypore fungi. In the current study, collections representing five different species belonging to two families, Postiaceae and Adustoporiaceae, were subjected to detailed morphoanatomical and molecular analyses. A combined matrix of two gene datasets (ITS and nrLSU) was analyzed using three different phylogenetic methods viz. Maximum Parsimony (MP), Maximum Likelihood (ML), and Bayesian inference (BI). Our study presents descriptions of five previously undocumented brown rot Polypore species from the country including Fuscopostia fragilis (Fr.) B.K. Cui, L.L. Shen & Y.C. Dai, Amaropostia stiptica (Pers.) B.K. Cui, L.L. Shen & Y.C. Dai, Cyanosporus piceicola B.K. Cui, L.L. Shen & Y.C. Dai, Spongiporus balsameus (Peck) A. David, Rhodonia placenta (Fr.) Niemelä, K.H. Larss. & Schigel. Regarding the molecular data, nodes of our subject sequences were substantially supported and fell under their respective species clades with high ML bootstrap values (≥ 95), MP bootstrap ≥ 74 and BI probabilities ≥ 0.98. Findings of the study will not only contribute to our understanding of local Polypores species diversity but also enhance knowledge of geographical distribution in global context.

Photosynthetic mechanisms of carbon fixation reduction in rice by cadmium and polycyclic aromatic hydrocarbons.

Environmental pollutants interfere with plant photosynthesis, thus reduce the crop yield and carbon storage capacity of farmland. This study comparatively explored the effects and mechanisms of polycyclic aromatic hydrocarbons (PAHs, e.g., phenanthrene, pyrene, and benzo[a]pyrene) and cadmium (Cd) on the carbon fixation capacity of rice throughout the growth period. Cd posed severer inhibition on the net carbon fixation of rice than PAHs, with the inhibition rates of 1.40-14.8-fold over PAHs at the concentrations of 0.5 or 5 mg/kg soil. Ribulose diphosphate carboxylase/oxygenase (Rubisco) involved in the Calvin cycle was identified as the common target of these pollutants to inhibit the photosynthetic carbon fixation. Further investigation demonstrated that the different inhibitory effects of Cd and PAHs was resulted from their different interference on the dual catalysis function (carboxylation and oxygenation) of Rubisco. Cd disturbed the balance of the intercellular CO2/O2, thus promoting the oxygenation and inhibiting the carboxylation of the substrate of Rubisco. Under the stress of Cd, the downstream metabolites (e.g. glycolate, glyoxylate, and serine) of Rubisco oxygenation were upregulated by over 2.01-3.24-fold, whereas the carboxylation efficiency (Vcmax) was decreased by 5.58-29.3%. Comparatively, PAHs inhibited both the carboxylation and oxygenation by down-regulating the expression of Rubisco coding gene (OsRBCS2, Log2FC < -2). This study broadens the understanding of the mechanisms of different environmental pollutants on the carbon fixation, providing valuable information for the quantitative estimation of their impacts on the farmland carbon sink. The results would be constructive to develop strategies for eliminating the adverse effects of contaminants and assist the carbon-neutral programs.

Exploring the potential of roof greening for low-carbon landscapes.

As one type of urban artificial ecosystems, roof greening exhibits carbon source/sink characteristics during their life cycle. The carbon cycle mechanism is complex. The lack of exhaustive carbon performance quantification methods and assessment indicators hinders the promotion and implementation of green roof urban decarboni-zation. Focusing on the quantification of roof greening low-carbon landscape potential, we analyzed the internal carbon cycle mechanism of green roof systems and explored four carbon reduction and sink pathways (P1-P4): biogenic carbon sink, embodied carbon, operational carbon, and bioenergy supply. Based on the dual performance indicators of normalized value of carbon emissions and carbon payback time, we summarized the normalized value measurement method of each pathway. The potential and characteristics of each pathway were quantified by extracting data from the literature. The results showed that the quantified potential values for P1 to P4 were 9.54, -2.26, 2.96 and 0.35 kg CO2·m-2·a-1, respectively, and that the potential values for each pathway were strongly influenced by plant types, climate, and other factors. The imperfect base database and the heterogeneity of assessment scenarios impacted the accuracy of the measurements. The integrated low carbon landscape potential of extensive green roofs was discussed in sub-scenarios, with the 40-year-life cycle integrated carbon reduction ranging from 92.24 to 433.42 kg CO2·m-2 and the carbon payback period ranging from 5 to 14 years. Finally, we summarized the problems in the assessment to facilitate future updates and improvements.

Authigenic mineral phases as a driver of the upper-ocean iron cycle.

Iron is important in regulating the ocean carbon cycle1. Although several dissolved and particulate species participate in oceanic iron cycling, current understanding emphasizes the importance of complexation by organic ligands in stabilizing oceanic dissolved iron concentrations2-6. However, it is difficult to reconcile this view of ligands as a primary control on dissolved iron cycling with the observed size partitioning of dissolved iron species, inefficient dissolved iron regeneration at depth or the potential importance of authigenic iron phases in particulate iron observational datasets7-12. Here we present a new dissolved iron, ligand and particulate iron seasonal dataset from the Bermuda Atlantic Time-series Study (BATS) region. We find that upper-ocean dissolved iron dynamics were decoupled from those of ligands, which necessitates a process by which dissolved iron escapes ligand stabilization to generate a reservoir of authigenic iron particles that settle to depth. When this 'colloidal shunt' mechanism was implemented in a global-scale biogeochemical model, it reproduced both seasonal iron-cycle dynamics observations and independent global datasets when previous models failed13-15. Overall, we argue that the turnover of authigenic particulate iron phases must be considered alongside biological activity and ligands in controlling ocean-dissolved iron distributions and the coupling between dissolved and particulate iron pools.

Selenite affected photosynthesis of Oryza sativa L. exposed to antimonite: Electron transfer, carbon fixation, pigment synthesis via a combined analysis of physiology and transcriptome.

Selenium (Se) is a microelement that can counteract (a)biotic stresses in plants. Excess antimony (Sb) will inhibit plant photosynthesis, which can be alleviated by appropriate doses of Se but the associated mechanisms at the molecular levels have not been fully explored. Here, a rice variety (Yongyou 9) was exposed to selenite [Se(IV), 0.2 and 0.8 mg L-1] alone or combined with antimonite [Sb(III), 5 and 10 mg L-1]. When compared to the 10 mg L-1 Sb treatment alone, addition of Se in a dose-dependent manner 1) reduced the heat dissipation efficiency resulting from the inhibited donors, Sb concentrations in shoots and roots, leaf concentrations of fructose, H2O2 and O2•-; 2) enhanced heat dissipation efficiency resulting from the inhibited accepters value, concentrations of Chl a, sucrose and starch, and the enzyme activity of adenosine diphosphate glucose pyrophosphorylase, sucrose phosphate synthase, and sucrose synthase; but 3) did not alter gas exchange parameters, concentrations of Chl b and total Chl, enzyme activity of soluble acid invertase, and values of maximum P700 signal, photochemical efficiency of PSI and electron transport rate of PSI. Se alleviated the damage caused by Sb to the oxygen-evolving complex and promoted the transfer of electrons from QA to QB. When compared to the 10 mg L-1 Sb treatment alone, addition of Se 1) up-regulated genes correlated to synthesis pathways of Chl, carotenoid, sucrose and glucose; 2) disturbed signal transduction pathway of abscisic acid; and 3) upregulated gene expression correlated to photosynthetic complexes (OsFd1, OsFER1 and OsFER2).

An ATP-sensitive phosphoketolase regulates carbon fixation in cyanobacteria.

Regulation of CO2 fixation in cyanobacteria is important both for the organism and global carbon balance. Here we show that phosphoketolase in Synechococcus elongatus PCC7942 (SeXPK) possesses a distinct ATP-sensing mechanism, where a drop in ATP level allows SeXPK to divert precursors of the RuBisCO substrate away from the Calvin-Benson-Bassham cycle. Deleting the SeXPK gene increased CO2 fixation particularly during light-dark transitions. In high-density cultures, the Δxpk strain showed a 60% increase in carbon fixation and unexpectedly resulted in sucrose secretion without any pathway engineering. Using cryo-EM analysis, we discovered that these functions were enabled by a unique allosteric regulatory site involving two subunits jointly binding two ATP, which constantly suppresses the activity of SeXPK until the ATP level drops. This magnesium-independent ATP allosteric site is present in many species across all three domains of life, where it may also play important regulatory functions.

Natural iron fertilization by shallow hydrothermal sources fuels diazotroph blooms in the ocean.

Iron is an essential nutrient that regulates productivity in ~30% of the ocean. Compared with deep (>2000 meter) hydrothermal activity at mid-ocean ridges that provide iron to the ocean's interior, shallow (<500 meter) hydrothermal fluids are likely to influence the surface's ecosystem. However, their effect is unknown. In this work, we show that fluids emitted along the Tonga volcanic arc (South Pacific) have a substantial impact on iron concentrations in the photic layer through vertical diffusion. This enrichment stimulates biological activity, resulting in an extensive patch of chlorophyll (360,000 square kilometers). Diazotroph activity is two to eight times higher and carbon export fluxes are two to three times higher in iron-enriched waters than in adjacent unfertilized waters. Such findings reveal a previously undescribed mechanism of natural iron fertilization in the ocean that fuels regional hotspot sinks for atmospheric CO2.

Enhanced carbon dioxide fixation of Chlorella vulgaris in microalgae reactor loaded with nanofiber membrane carried iron oxide nanoparticles.

To improve the CO2 dissolution and carbon fixation in the process of microalgae capturing CO2 from flue gas, a nanofiber membrane containing iron oxide nanoparticles (NPsFe2O3) for CO2 adsorption was prepared, and coupled with microalgae utilization to achieve carbon removal. The performance test results showed that the largest specific surface area and pore size were 8.148 m2 g-1 and 27.505 Å, respectively, when the nanofiber membrane had 4% NPsFe2O3. Through CO2 adsorption experiments, it was found that the nanofiber membrane could prolong the CO2 residence time and increase CO2 dissolution. Then, the nanofiber membrane was used as a CO2 adsorbent and semifixed culture carrier in the Chlorella vulgaris culture process. The results showed that compared with the group without nanofiber membrane (0 layer), the biomass productivity, CO2 fixation efficiency and carbon fixation efficiency of Chlorella vulgaris with 2 layers of membranes increased by 1.4 times.

Composting pig manure with nano-zero-valent iron amendment: Insights into the carbon cycle and balance.

The effectiveness of nano-zero-valent-iron (NZVI) addition during composting of pig manure (PM) was investigated. Different dosages of NZVI were mixed with PM substrate during a 50 days composting process. The results revealed that the higher share of NZVI addition, the higher OM degradation rate is. On contrary, it was observed that the higher share of NZVI addition, the lower the fulvic acid and the humin degradation rate is. Meanwhile, NZVI amendment increased the CO2 and CH4 emissions by 29-47 % and 53-57 %, respectively. The in-depth analysis showed that NZVI addition increased the activity of Sphaerobacter and Luteimonas, which eventually led to the degradation of hard-to-degrade OM faster. Additionally, NZVI was found to increase the filtration of microorganisms, reducing the toxicity and hygiene of compost products. No significant improvement in humic substance enhancement was observed during composting with NZVI addition but improved OM degradation.

Mitochondria preserve an autarkic one-carbon cycle to confer growth-independent cancer cell migration and metastasis.

Metastasis is the most common cause of death in cancer patients. Canonical drugs target mainly the proliferative capacity of cancer cells, which leaves slow-proliferating, persistent cancer cells unaffected. Metabolic determinants that contribute to growth-independent functions are still poorly understood. Here we show that antifolate treatment results in an uncoupled and autarkic mitochondrial one-carbon (1C) metabolism during cytosolic 1C metabolism impairment. Interestingly, antifolate dependent growth-arrest does not correlate with decreased migration capacity. Therefore, using methotrexate as a tool compound allows us to disentangle proliferation and migration to profile the metabolic phenotype of migrating cells. We observe that increased serine de novo synthesis (SSP) supports mitochondrial serine catabolism and inhibition of SSP using the competitive PHGDH-inhibitor BI-4916 reduces cancer cell migration. Furthermore, we show that sole inhibition of mitochondrial serine catabolism does not affect primary breast tumor growth but strongly inhibits pulmonary metastasis. We conclude that mitochondrial 1C metabolism, despite being dispensable for proliferative capacities, confers an advantage to cancer cells by supporting their motility potential.

Role of subterranean microbiota in the carbon cycle and greenhouse gas dynamics.

Subterranean ecosystems play an active role in the global carbon cycle, yet only a few studies using indirect methods have focused on the role of the cave microbiota in this critical cycle. Here we present pioneering research based on in situ real-time monitoring of CO2 and CH4 diffusive fluxes and concurrent δ13C geochemical tracing in caves, combined with 16S microbiome analysis. Our findings show that cave sediments are promoting continuous CH4 consumption from cave atmosphere, resulting in a significant removal of 65% to 90%. This research reveals the most effective taxa and metabolic pathways in consumption and uptake of greenhouse gases. Methanotrophic bacteria were the most effective group involved in CH4 consumption, namely within the families Methylomonaceae, Methylomirabilaceae and Methylacidiphilaceae. In addition, Crossiella and Nitrosococcaceae wb1-P19 could be one of the main responsible of CO2 uptake, which occurs via the Calvin-Benson-Bassham cycle and reversible hydration of CO2. Thus, syntrophic relationships exist between Crossiella and nitrifying bacteria that capture CO2, consume inorganic N produced by heterotrophic ammonification in the surface of sediments, and induce moonmilk formation. Moonmilk is found as the most evolved phase of the microbial processes in cave sediments that fixes CO2 as calcite and intensifies CH4 oxidation. From an ecological perspective, cave sediments act qualitatively as soils, providing fundamental ecosystem services (e.g. nutrient cycling and carbon sequestration) with direct influence on greenhouse gas emissions.

[Effects of radiation changes on net ecosystem exchange of carbon dioxide in a middle subtropical Chinese fir plantation]. / 辐射变化对中亚热带杉木人工林净CO2交换的影响.

Total solar radiation is an important factor affecting carbon exchange in forest ecosystem. In order to understand the effects of radiation change on carbon exchange in Chinese fir plantation, long-term monitoring data of carbon dioxide flux and meteorological factors measured by open eddy covariance system and meteorological gradient observation system were used in this study. The clearness index (kt) was used to represent the condition of solar radiation. We analyzed the effects of kt on net ecosystem exchange of carbon dioxide (NEE) in the central subtropical Chinese fir plantation during the growing season (from April to October). The results showed that total solar radiation in clear sky was usually higher in the morning than that in the afternoon, and that NEE was lower in the morning than in the afternoon. Such difference in NEE reached the maximum when the solar elevation angle was about 50°. At the medium kt(0.42-0.52), carbon absorption of Chinese fir plantation was the strongest. The ave-rage maximum relative change of NEE in 10 years in different solar elevation angles ranged from 11.0% to 29.4%, while the minimum and maximum critical values appeared at 35°-40° and 45°-50°, respectively. When kt was at the moderate degree due to the existence of clouds, carbon absorption and diffuse photosynthetically active radiation of Chinese fir plantation reached the maximum, and the latter might be the main reason for the former. Moderate radiation condition with the presence of cloud clould promote NEE of Chinese fir plantation and lead to largest carbon absorption.

Carbon-negative production of acetone and isopropanol by gas fermentation at industrial pilot scale.

Many industrial chemicals that are produced from fossil resources could be manufactured more sustainably through fermentation. Here we describe the development of a carbon-negative fermentation route to producing the industrially important chemicals acetone and isopropanol from abundant, low-cost waste gas feedstocks, such as industrial emissions and syngas. Using a combinatorial pathway library approach, we first mined a historical industrial strain collection for superior enzymes that we used to engineer the autotrophic acetogen Clostridium autoethanogenum. Next, we used omics analysis, kinetic modeling and cell-free prototyping to optimize flux. Finally, we scaled-up our optimized strains for continuous production at rates of up to ~3 g/L/h and ~90% selectivity. Life cycle analysis confirmed a negative carbon footprint for the products. Unlike traditional production processes, which result in release of greenhouse gases, our process fixes carbon. These results show that engineered acetogens enable sustainable, high-efficiency, high-selectivity chemicals production. We expect that our approach can be readily adapted to a wide range of commodity chemicals.

Folic Acid, Folinic Acid, 5 Methyl TetraHydroFolate Supplementation for Mutations That Affect Epigenesis through the Folate and One-Carbon Cycles.

Methylation is an essential biochemical mechanism that is central to the transmission of life, and crucially responsible for regulating gametogenesis and continued embryo development. The methylation of DNA and histones drives cell division and regulation of gene expression through epigenesis and imprinting. Brain development and its maturation also depend on correct lipid methylation, and continued neuronal function depends on biogenic amines that require methylation for their synthesis. All methylation processes are carried out via a methyltransferase enzyme and its unique co-factor S-adenosylmethionine (SAM); the transfer of a methyl group to a target molecule results in the release of SAH (SA homocysteine), and then homocysteine (Hcy). Both of these molecules are toxic, inhibiting methylation in a variety of ways, and Hcy recycling to methionine is imperative; this is achieved via the one carbon cycle, supported by the folates cycle. Folate deficiency causes hyperhomocysteinaemia, with several associated diseases; during early pregnancy, deficiency interferes with closure of the neural tube at the fourth week of gestation, and nutraceutical supplementation has been routinely prescribed to prevent neural tube defects, mainly involving B vitamins, Zn and folates. The two metabolic pathways are subject to single nucleotide polymorphisms that alter their activity/capacity, often severely, impairing specific physiological functions including fertility, brain and cardiac function. The impact of three types of nutraceutical supplements, folic acid (FA), folinic acid (FLA) and 5 Methyl THF (MTHF), will be discussed here, with their positive effects alongside potentially hazardous secondary effects. The issue surrounding FA and its association with UMFA (unmetabolized folic acid) syndrome is now a matter of concern, as UMFA is currently found in the umbilical cord of the fetus, and even in infants' blood. We will discuss its putative role in influencing the acquisition of epigenetic marks in the germline, acquired during embryogenesis, as well as the role of FA in the management of cancerous disease.