Search Results (221)

Oxidative stress significantly contributes to the exacerbation of brain damage during cerebral ischemia-reperfusion injury (CIR/I). In our previous study, purified cornel iridoid glycoside (PCIG), consisting of morroniside (MOR) and loganin (LOG), showed neuroprotective effects against CIR/I. To further explore the antioxidative effects and underlying molecular mechanisms, we applied PCIG, MOR, and LOG to rats injured by middle cerebral artery occlusion/reperfusion (MCAO/R) as well as H₂O₂-stimulated PC12 cells. Additionally, the molecular docking analysis was performed to assess the interaction between the PCIG constituents and Kelch-like ECH-associated protein 1 (Keap1). The results showed that the treated rats experienced fewer neurological deficits, reduced lesion volumes, and lower cell death accompanied by decreased levels of malondialdehyde (MDA) and protein carbonyl, as well as increased activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). In H₂O₂-stimulated PC12 cells, the treatments decreased reactive oxygen species (ROS) production, mitigated mitochondrial dysfunction, and inhibited mitochondrial-dependent apoptosis. Moreover, the treatments facilitated Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) translocation into the nucleus and selectively increased the expression of NAD(P)H quinone oxidoreductase 1 (NQO-1) and heme oxygenase 1 (HO-1) through MOR and LOG, respectively. Both MOR and LOG demonstrated strong binding affinity to Keap1. These findings suggested that PCIG, rather than any individual components, might serve as a valuable treatment for ischemic stroke by activating the Nrf2/NQO-1 and Nrf2/HO-1 signaling pathway. Full article

Apples and Korean green chili peppers are rich in phytochemicals and recognized for their diverse bioactive properties. Given the potential to enhance these beneficial compounds, this study investigated the effects of mineral supplementation during cultivation on the antioxidant and antiproliferative activities of extracts from both crops. Mineral-enriched cultivation significantly increased the total phenolic and flavonoid contents in both crops, which was accompanied by enhanced DPPH and ABTS radical scavenging activities. Moreover, the mineral-supplemented extracts of Korean green chili pepper activated the Nrf2 signaling pathway and upregulated downstream antioxidant enzymes, including heme oxygenase-1 (HO-1), γ-glutamylcysteine ligase (GCL), and glutathione peroxidase (GPx). Notably, the mineral-supplemented Korean green chili pepper extract significantly suppressed the proliferation of human colorectal cancer cells. These findings suggest that mineral supplementation during cultivation may improve the functional quality of apples and Korean green chili peppers, supporting their potential application in cancer prevention and complementary therapeutic strategies. Full article

Large-conductance, voltage- and calcium-activated potassium (BK) channels are crucial regulators of cellular excitability, influenced by various signaling molecules, including heme. The BK channel contains a heme-sensitive motif located at the sequence ⁶¹²CKACH⁶¹⁶, which is a conserved heme regulatory motif (HRM) found in the cytochrome c protein family. This motif is situated within a linker region of approximately 120 residues that connect the RCK1 and RCK2 domains, and it also includes terminal α-helices similar to those found in cytochrome c family proteins. However, much of this region has yet to be structurally defined. We conducted a sequence alignment of the BK linker region with mitochondrial cytochrome c and cytochrome c domains from various hemoproteins to better understand this functionally significant region. In addition to the HRM motif, we discovered that important structural and functional elements of cytochrome c proteins are conserved in the BK RCK1-RCK2 linker. Firstly, the part of the BK region that is resolved in available atomic structures shows similarities in secondary structural elements with cytochrome c domain proteins. Secondly, the Met80 residue in cytochrome c domains, which acts as the second axial ligand to the heme iron, aligns with the BK channel. Beyond its role in electron shuttling, cytochrome c domains exhibit various catalytic properties, including peroxidase activity—specifically, the oxidation of suitable substrates using peroxides. Our findings reveal that the linker region endows human BK channels with peroxidase activity, showing an apparent H₂O₂ affinity approximately 40-fold greater than that of mitochondrial cytochrome c under baseline conditions. This peroxidase activity was reduced when substitutions were made at ⁶¹²CKACH⁶¹⁶ and other relevant sites. These results indicate that the BK channel possesses a novel module similar to the cytochrome c domains of hemoproteins, which may give rise to unique physiological functions for these widespread ion channels. Full article

The regulation of oxidative stress is an effective strategy for treating cancers. Therapeutic strategies for modulating an undesirable redox balance against cancers have included the enhancement of oxidative components, reducing the action of antioxidant systems, and the combined application of radiation and redox-modulating drugs. A precise understanding of redox regulation is required to treat different kinds of cancer. This review focuses on the redox regulation and oxidative stress defense systems of lung cancers. Thus, we highlighted several enzymatic antioxidant components, such as superoxide dismutase, catalase, heme oxygenase-1, peroxiredoxin, glutaredoxin, thioredoxin, thioredoxin reductase, glutathione peroxidase, and antioxidant components, including glutathione, nuclear factor erythroid 2–related factor 2, 8-oxo-7,8-dihydro-2′-deoxyguanosine, and mitochondrial citrate carrier SLC25A1, based on PubMed and Scopus-indexed literature. Understanding the oxidative stress defense system in lung cancer would be beneficial for developing and expanding therapeutic strategies, such as drug development, drug design, and advanced delivery platforms. Full article

This study evaluated the inhibitory activity of quercetin at sub-inhibitory concentrations on quorum-sensing (QS) molecules in vitro and the effects of dietary supplementation with quercetin (for 24 consecutive days) on enterotoxigenic Escherichia coli (ETEC)-induced inflammatory and oxidative stress responses in weaned piglets. The piglets were fed one of three diets: the basal diet (Con), ETEC challenge (K88) after the basal diet, or ETEC challenge (quercetin + K88) after the basal diet supplemented with 0.2% quercetin. In vitro experiments revealed that 5 mg/mL quercetin exhibited the strongest QS inhibitory activity and reduced pigment production by Chromobacterium violaceum ATCC12472 by 67.70%. In vivo experiments revealed that quercetin + K88 significantly increased immunoglobulin A (IgA), immunoglobulin M (IgM), and immunoglobulin G (IgG) levels in the serum, ileum mucosa, and colon mucosa; increased glutathione peroxidase (GSH-Px), catalase (CAT), and superoxide dismutase (SOD) levels in the serum, liver, and colon mucosa; and decreased cluster of differentiation 3 (CD3) and cluster of differentiation 8 (CD8)activity in the serum compared with K88 alone. Quercetin + K88 significantly alleviated pathological damage to the liver and spleen and upregulated antioxidant genes (nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1(HO-1), CAT, SOD, and glutathione s-transferase (GST)). Inducible nitric oxide synthase (iNOS) and kelch-like ech-associated protein 1 (Keap1), which cause oxidative damage to the liver and spleen, were significantly downregulated. The acetic acid content in the cecum was significantly increased, and the E. coli count and QS signal molecule autoinducer-2 (AI-2) yield were significantly reduced. In conclusion, 0.2% dietary quercetin can alleviate ETEC-induced inflammation and oxidative stress in weaned piglets. Full article

Oxidative stress, which contributes to neuronal cell dysfunction, is a critical factor in the pathogenesis of neurodegenerative diseases. Anthocyanins and α-tocopherol have shown potential in mitigating oxidative damage, and their combination may provide synergistic effects. This study investigated the combined effects of a cyanidin-3-glucoside (C3G)-enriched extract derived from Oryza sativa L. cv. RD83 and α-tocopherol (C3GE) on hydrogen peroxide (H₂O₂)-induced oxidative stress in SH-SY5Y cells. Cells were treated with C3GE during exposure to 200 µM H₂O₂. Cell viability, intracellular reactive oxygen species (ROS), and oxidative stress biomarkers, including the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px), as well as malondialdehyde (MDA) levels, were evaluated. Protein expression levels of histone deacetylase 1 (HDAC1), nuclear factor erythroid 2 related factor 2 (Nrf2), heme oxygenase 1 (HO-1), and SOD1 were also assessed. The combined treatment markedly improved cell viability, suppressed ROS accumulation, enhanced antioxidant enzyme activities, and significantly reduced MDA levels, suggesting effective protection against oxidative damage. Mechanistically, C3GE downregulated HDAC1 expression while upregulating Nrf2, HO-1, and SOD1, indicating that its antioxidant and neuroprotective effects are mediated, at least in part, through epigenetic modulation of redox-related signaling pathways. These results demonstrate a synergistic interaction between C3G and α-tocopherol that enhances cellular antioxidant defenses and supports redox homeostasis. In conclusion, the C3GE combination offers a promising therapeutic approach for preventing or attenuating oxidative stress-induced neuronal injury, with potential relevance for the treatment of neurodegenerative disorders. Full article

Lactoperoxidase (LPO) (E.C. 1.11.1.7) is a member of the superfamily of mammalian heme peroxidases that is isolated from milk, and it is the first enzyme announced to be found in milk. In addition to milk, LPO is also found in saliva, tears, and airways (airway goblet cells and submucosal glands). It contributes significantly to the self-defense of the mammal body. It catalyzes the oxidation of certain molecules such as thiocyanate (SCN⁻), I⁻, and Br⁻ in the presence of hydrogen peroxide (H₂O₂). This reaction leads to the formation of antimicrobial products that have a great antimicrobial spectrum, including antibacterial, antiviral, and antifungal activity, especially hypothiocyanite (OSCN⁻) and hypoiodite (OI⁻), which are coming into prominence via their high antimicrobial activity. The lactoperoxidase system (LPOS) is the system consisting of LPO, H₂O₂, and SCN⁻. LPO has a great potential to be used in various areas such as preservation and shelf-life elongation of milk; milk products; meat; meat products; plants, including fruits and vegetables; and oral care, diagnosis, immunomodulation, and treatment of nephrotoxicity. The LPO gene, along with LPO itself, is important for animals. In the absence of the LPO gene, there is an increase in the frequency of diverse diseases, including inflammation, tumor formation, and obesity. In this review, we mentioned general information about the enzyme LPO and its potential. Chemical properties and other features of other components of the LPOS, H₂O₂, and SCN⁻ were also touched on the review. To offer readers a comprehensive understanding of the enzyme’s biological significance and research progress over time, both recent and older studies have been used together. Lastly, we discussed potential applications of LPO in different areas and left future remarks in the light of recent studies. Full article

Busulfan (BU) is a widely used chemotherapy drug that has been shown to cause reproductive functional impairment in humans and model animals. However, the precise mechanisms underlying testicular injury induced by BU exposure have not been fully elucidated. Ferroptosis is a form of programmed cell death mediated by iron-dependent lipid peroxidation. The aim of the current study was to determine whether ferroptosis was involved in BU-induced testicular injury. We demonstrated that exposure to BU led to an increase in iron content in the testes of mice. Subsequent western blotting and reverse transcription quantitative PCR, as well as staining of testicular tissue sections, confirmed that ferroptosis mediated BU-induced testicular injury. Consistent with our in vivo findings, we found that ferroptosis, including iron metabolism and the solute carrier family 7 member 11/glutathione peroxidase 4 (xCT/GPX4) signaling pathway, may play a key role in mediating BU-induced injury to GC-1 spg cells in vitro. Treatment with ferroptosis inhibitors slowed cell death caused by BU exposure. Specifically, we found that the administration of zinc protoporphyrin IX (ZnPP), a heme oxygenase 1 (HO1) inhibitor, rescued BU-induced cell death. In conclusion, our in vivo and in vitro findings confirmed that BU exposure led to testicular ferroptosis in mice via the iron intake pathway and the HO1 signaling pathway. Full article

Sickle cell disease (SCD) is a monogenic blood disorder characterized by abnormal hemoglobin S production, which polymerizes under hypoxia conditions to produce chronic red blood cell hemolysis, widespread organ damage, and vasculopathy. As a result of vaso-occlusion and ischemia-reperfusion injury, individuals with SCD have recurrent pain episodes, infection, pulmonary disease, and fall victim to early death. Oxidative stress due to chronic hemolysis and the release of hemoglobin and free heme is a key driver of the clinical manifestations of SCD. The net result is the generation of reactive oxygen species that consume nitric oxide and overwhelm the antioxidant system due to a reduction in enzymes such as superoxide dismutase and glutathione peroxidase. The primary mechanism for handling cellular oxidative stress is the activation of antioxidant proteins by the transcription factor NRF2, a promising target for treatment development, given the significant role of oxidative stress in the clinical severity of SCD. In this review, we discuss the role of oxidative stress in health and the clinical complications of SCD, and the potential of NRF2 as a treatment target, offering hope for developing effective therapies for SCD. This task requires our collective dedication and focus. Full article

Sickle cell disease (SCD) is an inherited hemoglobin disorder that is widespread across the globe. It is characterized by a very complex pathogenesis, but at the basis of the disease is the mutation of the HBB gene, which determines the production of a mutated hemoglobin: sickle cell hemoglobin (HbS). The polymerization of HbS, which occurs when the protein is in a deoxygenated state, and the greater fragility of sickle cell red blood cells (sRBCs) determine the release of iron, free heme, and HbS in the blood, favoring oxidative stress and the production of reactive oxygen species (ROS). These features are common to the features of a new model of cell death known as ferroptosis, which is characterized by the increase of iron and ROS concentrations and by the inhibition of glutathione peroxidase 4 (GPx4) and the System Xc⁻. In this context, this review aims to discuss the potential molecular and biochemical pathways of ferroptosis involved in SCD, aiming to highlight possible tags involved in treating the disease and inhibiting ferroptosis. Full article

Objectives: Ischemic stroke is a severe neurological disorder with high morbidity, mortality, and disability rates, posing a substantial burden on patients, families, and healthcare systems. Soy isoflavone (SI), a naturally occurring phytoestrogen, has demonstrated promising neuroprotective effects. This study aimed to evaluate the anti-stroke efficacy of SI and elucidate its underlying mechanisms through integrated phytochemical profiling, network pharmacology, and both in vitro and in vivo experimental validation. Methods: Active constituents of SI were extracted via reflux and identified using liquid chromatography–mass spectrometry (LC-MS). Network pharmacology was employed to predict therapeutic targets and signaling pathways. The neuroprotective effects of SI were first assessed in PC12 cells subjected to oxygen–glucose deprivation/reoxygenation (OGD/R) injury in vitro. For in vivo evaluation, transient cerebral ischemia–reperfusion injury was induced using the bilateral common carotid artery occlusion (BCCAO) model in adult male ICR rats (27.3 ± 1.8 g; 6–8 weeks old), obtained from the Shanghai Experimental Animal Center, Chinese Academy of Sciences. Forty-eight rats were randomly assigned into four groups (n = 12): sham, model (BCCAO), SI-treated (100 mg/kg, oral gavage for 5 days), and edaravone (EDA)-treated (10 mg/kg, i.p., positive control). All procedures were approved by the Institutional Animal Care and Use Committee of Changchun Normal University (Approval No. 2024003, 13 March 2024) and conducted in accordance with the NIH guidelines and ARRIVE 2.0 reporting standards. Results: In vitro, SI significantly enhanced PC12 cell viability from 57.23 ± 2.88% to 80.76 ± 4.43% following OGD/R. It also reduced intracellular Ca²⁺ by 58.42%, lactate dehydrogenase (LDH) release by 37.67%, caspase-3 activity by 55.05%, and reactive oxygen species (ROS) levels by 74.13% (p < 0.05). A flow cytometry analysis revealed that OGD/R increased the apoptosis rate from 5.34% (control) to 30.85% (model group), which was significantly attenuated by SI treatment, especially in the 560 µg/mL group (20.00%), followed by the 140 and 280 µg/mL groups. In vivo, SI improved neurological scores from 8.3 ± 1.09 to 6.8 ± 1.68, reduced cerebral infarction volume by 18.49%, and alleviated brain edema by 10.42% (p < 0.05). SI also decreased malondialdehyde (MDA) and LDH levels by 31.15% and 39.46%, respectively, while increasing the activity of antioxidant enzymes: superoxide dismutase (SOD) by 11.70%, catalase (CAT) by 26.09%, and glutathione peroxidase (GSH-px) by 27.55% (p < 0.01). Scratch assay results showed that SI restored the impaired migratory ability of the OGD/R-treated PC12 cells, further supporting its role in cellular repair. A Western blot analysis demonstrated the upregulation of nuclear factor erythroid 2–related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and NAD(P)H:quinone oxidoreductase 1 (NQO1) and the downregulation of Kelch-like, ECH-associated protein 1 (Keap1) in the cerebral ischemia–reperfusion model. Conclusions: These findings indicate that soy isoflavone confers significant neuroprotective effects against cerebral ischemia–reperfusion injury by enhancing endogenous antioxidant defense mechanisms, reducing oxidative stress, inhibiting apoptosis, and promoting cell migration. The protective effects are likely mediated through the activation of the Nrf2/Keap1 signaling pathway, supporting the therapeutic potential of SI in ischemic stroke treatment. Full article

OP, a systemic bone disorder marked by reduced bone mass and heightened fracture risk, poses a significant global health burden, particularly among aging populations. Current treatments, including bisphosphonates and calcium supplementation, are limited by adverse effects and incomplete efficacy. Emerging research highlights ferroptosis—an iron-dependent cell death driven by lipid peroxidation—as a critical contributor to OP pathogenesis, characterized by dysregulated iron metabolism, oxidative stress, and lipid peroxide accumulation, which disrupt bone remodeling by impairing osteoblast function and enhancing osteoclast activity. This review elucidates the mechanistic interplay between ferroptosis and OP subtypes (diabetic osteoporosis (DOP), glucocorticoid-induced (GIOP), and postmenopausal osteoporosis (PMOP)) and evaluates the efficacy of Chinese herbal interventions in mitigating ferroptosis-driven bone loss. Key findings reveal that excess iron exacerbates lipid peroxidation via the Fenton reaction, while glutathione peroxidase 4 (GPX4) inactivation and system Xc- inhibition amplify oxidative damage. In DIOP, hyperglycemia-induced ROS and advanced glycation end products suppress osteogenesis, countered by melatonin and naringenin via nuclear factor -related factor 2 (Nrf2)/GPX4 activation. GIOP involves dexamethasone-mediated GPX4 downregulation, mitigated by exosomes and melatonin through phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling. PMOP driven by estrogen deficiency-induced iron overload is alleviated by aconitine and icariin (ICA) via nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and signal transducer and activator of transcription 3 (STAT3) pathways. Chinese herbs, including active compounds (quercetin, gastrodin, ICA, etc.) and formulations (Bugu Shengsui Capsule, Erxian Decoction (EXD), etc.), regulate iron metabolism, enhance antioxidant defenses (Nrf2/heme oxygenase 1(HO-1)), and inhibit lipid peroxidation, effectively restoring bone homeostasis. These findings underscore ferroptosis as a pivotal mechanism in OP progression and highlight the therapeutic promise of Chinese herbs in bridging traditional medicine with modern mechanistic insights. Future research should prioritize elucidating precise molecular targets, optimizing formulations, and validating clinical efficacy to address current therapeutic gaps. Full article

Background/Objectives: Some G-quadruplex (G4)-forming nucleic acid sequences bind a hemin cofactor to enhance its peroxidase-like activity. This has been implemented in a variety of bioanalytical assays benefiting from analyte-dependent peroxidation of a chromogenic organic substrate (e.g., ABTS) to produce a color change. Adenine and cytosine nucleotides in the vicinity of the G4 hemin-binding site promote the peroxidation reaction. In this work, the effect of G4 loop and flanking nucleotides on the colorimetric signal of split hybridization probes utilizing hemin-G4 signal reporters was tested. Methods: G4s varying by loop sequences and flanking nucleotides were tested with hemin for ABTS peroxidation (A₄₂₀), and the signal was compared with that produced by the most catalytically efficient complexes reported in the literature using one-way ANOVA and post hoc pairwise comparison with Tukey’s HSD test. The best G4s were used as signal transducers in the split peroxidase deoxyribozyme (sPDz) probes for sensing two model nucleic acid analytes, as well as in a cascade system, where the analyte-dependent assembly of an RNA-cleaving deoxyribozyme 10–23 results in G4 release. Results: Intramolecular G4s (G₃T)₃G₃TC or G₃T₃G₃ATTG₃T₃G₃ were found to be the most efficient hemin PDzs. When splitting intramolecular G4 for the purpose of sPDz probe design, the addition of a flanking d(TC) sequence at one of the G4 halves or d(ATT) in a loop connecting the second and third G-tracts helps boost analyte-dependent signal intensity. However, for the cascade system, the effect of d(TC) or d(ATT) in the released G4 was not fully consistent with the data reported for intramolecular G4-hemin complexes. Conclusions: Our findings offer guidance on the design of split hybridization probes utilizing the peroxidase-like activity of G4-hemin complexes as a signal transducer. Full article

Background/Objectives: Deoxynivalenol (DON), known as vomitoxin, is one of the most common mycotoxins produced by Fusarium graminearum, with high detection rates in feed worldwide. Ferroptosis is a novel mode of cell death characterized by lipid peroxidation and the accumulation of reactive oxygen species. Although it has been demonstrated that DON can induce ferroptosis in the liver, the specific mechanisms and pathways are still unknown. The aim of this experiment was to investigate that DON can induce iron metabolism disorders in the livers of mice, thereby triggering ferroptosis and causing toxic damage to the liver. Methods: Male C57 mice were treated with DON at a 5 mg/kg BW concentration as an in vivo model. After sampling, organ coefficient monitoring, liver function test, histopathological analysis, liver Fe²⁺ content test, and oxidative stress-related indexes were performed. The mRNA and protein expression of Nrf2 and its downstream genes were also detected using a series of methods including quantitative real-time PCR, immunofluorescence double-labeling, and Western blotting analysis. Results: DON can cause damage to the liver of a mouse. Specifically, we found that mouse livers in the DON group exhibited pathological damage in cell necrosis, inflammatory infiltration, cytoplasmic vacuolization, elevated relative liver weight, and significant changes in liver function indexes. Meanwhile, the substantial reduction in the levels of glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), and total antioxidant capacity (T-AOC) in the DON group indicated that DON also caused oxidative stress in the liver. Notably, DON exposure increased the levels of Fe²⁺ and Malondialdehyde (MDA) in the liver, which provides strong evidence for the occurrence of iron metabolism and ferroptosis disorders. Most importantly, mRNA and protein expression of Nrf2, an important pathway for iron metabolism and ferroptosis, along with its downstream genes, heme oxygenase (HO-1), quinone oxidoreductase (NQO1), glutathione peroxidase (GPX4), and solute carrier gene (SLC7a11), were significantly inhibited in the DON group. Conclusions: Based on our results, the Nrf2 pathway is closely associated with DON-induced iron metabolism disorders and ferroptosis in mouse livers, suggesting that maintaining hepatic iron homeostasis and activating the Nrf2 pathway may be a potential target for mitigating DON hepatotoxicity in the future. Full article

Background: Heme is an important cofactor and plays crucial roles in the correct folding of hemoproteins. The synthesis of heme can be enhanced by the plasmid-based expression of heme biosynthetic genes. However, plasmid-based expression is genetically unstable and requires the utilization of antibiotics to maintain high copy numbers of plasmids. Methods: The rate-limiting steps in heme biosynthesis were first analyzed based on previous studies and the accumulation of heme intermediates was achieved by adding heme precursor (5-aminolevulinic acid, ALA). Next, the intracellular accumulation of porphyrin was increased by deleting the porphyrin transporter TolC. Finally, the heme synthetic genes were modified by integrating the hemA and hemL genes into the cheW and yciQ locus, assembling the rate-limiting enzymes HemC and HemD with RIAD-RIDD tags, replacing the promoters of hemE/hemH genes with the constitutive promoter P_J23100, and deleting the heme degradation gene yfeX. Results: An enhanced heme supply HEME2 strain was obtained with a heme titer of 0.14 mg/L, which was 4.60-fold higher than that of the C41(DE3) strain. The HEME2 strain was applied to produce human hemoglobin and leghemoglobin. The titer and peroxidase activity of human hemoglobin were 1.29-fold and 42.4% higher in the HEME2-hHb strain than the values in the control strain C41-hHb. In addition, the peroxidase activity and heme content of leghemoglobin were increased by 39.2% and 53.4% in the HEME2-sHb strain compared to the values in the control strain C41-sHb. Conclusions: A plasmid-free Escherichia coli C41(DE3) strain capable of efficient and stable heme supply was constructed and can be used for the production of high-active hemoglobins. Full article