NMNH: 1. “Bonzyme” Whole-enzymatic method, environmental-friendly, no harmful solvent residues manufacturing powder. 2. Bontac is a very first manufacture in the world to produce the NMNH powder on the level of high purity, stability. 3. Exclusive “Bonpure” seven-step purification technology, high purity(up to 99%) and stability of production of NMNH powder 4. Self-owned factories and obtained a number of international certifications to ensure high quality and stable supply of products of NMNH powder 5. Provide one-stop product solution customization service
NADH: 1. Bonzyme whole-enzymatic method, environmental-friendly, no harmful solvent residues 2. Exclusive Bonpure seven-step purification technology, purity up higher than 98 % 3. Special patented process crystal form, higher stability 4. Obtained a number of international certifications to ensure high quality 5. 8 domestic and foreign NADH patents, leading the industry 6. Provide one-stop product solution customization service
NAD: 1. “Bonzyme” Whole-enzymatic method, environmental-friendly, no harmful solvent residues 2. Stable supplier of 1000+ enterprises around the world 3. Unique “Bonpure” seven-step purification technology, higher product content and higher conversion rate 4. Freeze drying technology to ensure stable product quality 5. Unique crystal technology, higher product solubility 6. Self-owned factories and obtained a number of international certifications to ensure high quality and stable supply of products
NMN: 1. “Bonzyme”Whole-enzymatic method, environmental-friendly, no harmful solvent residues 2. Exclusive“Bonpure”seven-step purification technology, high purity(up to 99.9%) and stability 3. Industrial leading technology: 15 domestic and international NMN patents 4. Self-owned factories and obtained a number of international certifications to ensure high quality and stable supply of products 5. Multiple in vivo studies show that Bontac NMN is safe and effective 6. Provide one-stop product solution customization service 7. NMN raw material supplier of famous David Sinclair team of Harvard University
Bontac Bio-Engineering (Shenzhen) Co., Ltd. (hereafter referred to as BONTAC) is a high-tech enterprise established in July 2012. BONTAC integrates R&D, production and sales, with enzyme catalysis technology as the core and coenzyme and natural products as main products. There are six major series of products in BONTAC, involving coenzymes, natural products, sugar substitutes, cosmetics, dietary supplements and medical intermediates.
As the leader of the global NMN industry, BONTAC has the first whole-enzyme catalysis technology in China. Our coenzyme products are widely used in health industry, medical & beauty, green agriculture, biomedicine and other fields. BONTAC adheres to independent innovation, with more than 170 invention patents. Different from the traditional chemical synthesis and fermentation industry, BONTAC has advantages of green low-carbon and high-value-added biosynthesis technology. What’s more, BONTAC has established the first coenzyme engineering technology research center at the provincial level in China which also is the sole in Guangdong Province.
In the future, BONTAC will focus on its advantages of green, low-carbon and high-value-added biosynthesis technology, and build ecological relationship with academia as well as upstream/downstream partners, continuously leading the synthetic biological industry and creating a better life for human beings.
1. "Bonzyme" Whole-enzymatic method, environmental-friendly, no harmful solvent residues manufacturing powder.
2. Bontac is a very first manufacture in the world to produce the NMNH powder on the level of high purity, stability.
3. Exclusive “Bonpure” seven-step purification technology, high purity (up to 99%) and stability of production of NMNH powder
4. Self-owned factories and obtained a number of international certifications to ensure high quality and stable supply of products of NMNH powder
5. Provide one-stop product solution customization service
The main methods of NMNH powder preparation include extraction, fermentation, fortification, biosynthesis and organic matter synthesis. Compared with other preparations, the whole enzyme becomes the mainstream method owing to the advantages of pollution free, high level of purity and
When applied to cultured cells, the NMNH is shown to be more efficient than NMN as it was able to “significantly increase NAD+ at a ten times lower concentration (5 µM) than that needed for NMN”. Moreover, NMNH shows to be more effective , as at 500 µM concentration, it achieved “an almost 10-fold increase in the NAD+ concentration, while NMN was only able to double NAD+ content in these cells, even at 1 mM concentration.”.
Interestingly, NMNH also appears to act quicker and has a longer-lasting effect compared to NMN. According to the authors, NMNH induces a “significant increase in NAD+ levels within 15 minutes”, and “NAD+ steadily increased for up to 6 hours and remained stable for 24 hours, while NMN reached its plateau after only 1 hour, most likely because the NMN recycling pathways to NAD+ had already become saturated.”.
NADH is synthesized by the body and thus is not an essential nutrient. It does require the essential nutrient nicotinamide for its synthesis, and its role in energy production is certainly an essential one. In addition to its role in the mitochondrial electron transport chain, NADH is produced in the cytosol. The mitochondrial membrane is impermeable to NADH, and this permeability barrier effectively separates the cytoplasmic from the mitochondrial NADH pools. However, cytoplasmic NADH can be used for biologic energy production. This occurs when the malate-aspartate shuttle introduces reducing equivalents from NADH in the cytosol to the electron transport chain of the mitochondria. This shuttle mainly occurs in the liver and heart.
Nicotinamide adenine dinucleotide (NAD+ ) homeostasis is constantly compromised due to degradation by NAD+ -dependent enzymes. NAD+ replenishment by supplementation with the NAD+ precursors nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR) can alleviate this imbalance. However, NMN and NR are limited by their mild effect on the cellular NAD+ pool and the need of high doses. Here, we report a synthesis method of a reduced form of NMN (NMNH), and identify this molecule as a new NAD+ precursor for the first time. We show that NMNH increases NAD+ levels to a much higher extent and faster than NMN or NR, and that it is metabolized through a different, NRK and NAMPT-independent, pathway. We also demonstrate that NMNH reduces damage and accelerates repair in renal tubular epithelial cells upon hypoxia/reoxygenation injury. Finally, we find that NMNH administration in mice causes a rapid and sustained NAD+ surge in whole blood, which is accompanied by increased NAD+ levels in liver, kidney, muscle, brain, brown adipose tissue, and heart, but not in white adipose tissue. Together, our data highlight NMNH as a new NAD+ precursor with therapeutic potential for acute kidney injury, confirm the existence of a novel pathway for the recycling of reduced NAD+ precursors and establish NMNH as a member of the new family of reduced NAD+ precursors.
First, inspect the factory. After some screening, NMNH companies that directly face consumers pay more attention to brand building. Therefore, for a good brand, quality is the most important thing, and the first thing to control the quality of raw materials is to inspect the factory. Bontac company actually manufacturing NMNH powder of high quality with the caterias of SGS. Secondly, the purity is tested. Purity is one of the most important parameters of NMN powder. If high purity NMNH cannot be guaranteed, the remaining substances are likely to exceed the relevant standards. As the attached certificates demonstrates that the NMNH powder produced by Bontac reach the purity of 99%. Finally, a professional test spectrum is needed to prove it. Common methods for determining the structure of an organic compound include Nuclear Magnetic Resonance Spectroscopy (NMR) and high-resolution mass spectrometry (HRMS). Usually through the analysis of these two spectra, the structure of the compound can be preliminarily determined.
On August 10, 2021, researchers from Shanghai University of Science and Technology published an article titled NAD+ supplement potentiates tumor killing function by rescuing defective TUBBY-mediated NAMPT transcription in tumor infiltrated T cells in Cell Reports, revealing that NAD+ in supplemented during CAR-T therapy and immune checkpoint inhibitor therapy, it can improve the anti-tumor activity of T. At present, the supplementary precursor of NAD+, as a nutritional product,has been verified for human consumption safety.This achievement provides a simply and feasible new method for improving the anti-tumor activity of T cells. Cancer immunotherapies including the adoptive transfer of naturally occurring tumor-infiltrating lymphocytes (TILs) and genetically engineered T cells, as well as the use of immune checkpoint blockade (ICB) to boost the function of T cells, have emerged as promising approaches to achieve durable clinical responses of otherwise treatment-refractory cancers (Lee et al., 2015; Rosenberg and Restifo, 2015; Sharma and Allison, 2015). Although immunotherapies have been successfully used in the clinic, the number of patients benefiting from them is still limited (Fradet et al., 2019; Newick et al., 2017). Tumor microenvironment (TME)-related immunosuppression has emerged as the major reason for low and/or no response to both immunotherapies (Ninomiya et al., 2015; Schoenfeld and Hellmann, 2020). Therefore, efforts to investigate and overcome TME-related limitations in immune therapies are of great urgency. The fact that immune cells and cancer cells share many fundamental metabolic pathways implies an irreconcilable competition for nutrients in TME (Andrejeva and Rathmell, 2017; Chang et al., 2015). During uncontrolled proliferation, cancer cells hijack alternative pathways for more rapid metabolite generation (Vander Heiden et al., 2009). As a consequence, nutrient depletion, hypoxia, acidity, and generation of metabolites that can be toxic in the TME may hinder successful immunotherapy (Weinberg et al., 2010). Indeed, TILs often experience mitochondrial stress within growing tumors and become exhausted (Scharping et al., 2016). Interestingly, multiple studies also indicate that metabolic changes in TME could re-shape T cell differentiation and functional activity (Bailis et al., 2019; Chang et al., 2013; Peng et al., 2016). All these evidences inspired us to hypothesize that metabolic reprogramming in T cells might rescue them from a stressed metabolic environment, thereby reinvigorating their anti-tumor activity (Buck et al., 2016; Zhang et al., 2017). In this current study, by integrating both genetic and chemical screens, we identified that NAMPT, a key gene involved in NAD+ biosynthesis, was essential for T cell activation. NAMPT inhibition led to robust NAD+ decline in T cells, thereby disrupting glycolysis regulation and mitochondrial function, blocking ATP synthesis, and dampening the T cell receptor (TCR) downstream signaling cascade. Building on the observation that TILs have relatively lower NAD+ and NAMPT expression levels than T cells from peripheral blood mononuclear cells (PBMCs) in ovarian cancer patients, we performed genetic screening in T cells and identified that Tubby (TUB) is a transcription factor for NAMPT. Finally, we applied this basic knowledge in the (pre) clinic and showed very strong evidence that supplementation with NAD+ dramatically improves the anti-tumor killing activity both in adoptively transferred CAR-T cells therapy and immune check point blockade therapy, indicating their promising potential for targeting NAD+ metabolism to better treat cancers. 1.NAD+ regulates the activation of T cells by affecting energy metabolism After antigen stimulation, T cells undergo metabolic reprogramming, from mitochondrial oxidation to glycolysis as the main source of ATP. While maintaining sufficient mitochondrial functions to support cell proliferation and effector functions.Given that NAD+ is the main coenzyme for redox, the researchers verified the effect of NAD+ on the level of metabolism in T cells through experiments such as metabolic mass spectrometry and isotope labeling. The results of in vitro experiments show that NAD+ deficiency will significantly reduce the level of glycolysis, TCA cycle and electron transport chain metabolism in T cells. Through the experiment of replenishing ATP, the researchers found that the lack of NAD+ mainly inhibits the production of ATP in T cells, thereby reducing the level of T cell activation. 2.The NAD+ salvage synthesis pathway regulated by NAMPT is essential for T cell activation The metabolic reprogramming process regulates the activation and differentiation of immune cells. Targeting T cell metabolism provides an opportunity to modulate the immune response in a cellular way. Immune cells in the tumor microenvironment, their own metabolic level will also be correspondingly affected. The researchers in this article have discovered the important role of NAMPT in the activation of T cells through genome-wide sgRNA screening and metabolism-related small molecule inhibitor screening experiments. Nicotinamide adenine dinucleotide (NAD+) is a coenzyme for redox reactions and can be synthesized through the salvage pathway, de novo synthesis pathway, and Preiss-Handler pathway. The NAMPT metabolic enzyme is mainly involved in the NAD+ salvage synthesis pathway. Analysis of clinical tumor samples found that in tumor-infiltrating T cells, their NAD+ levels and NAMPT levels were lower than other T cells. Researchers speculate that NAD+ levels may be one of the factors that affect the anti-tumor activity of tumor-infiltrating T cells. 3.Supplement NAD+ to enhance the anti-tumor activity of T cells Immunotherapy has been exploratory research in cancer treatment, but the main problem is the best treatment strategy and the effectiveness of immunotherapy in the overall population. Researchers want to study whether enhancing the activation ability of T cells by supplementing NAD+ levels can enhance the effect of T cell-based immunotherapy. At the same time, in the anti-CD19 CAR-T therapy model and anti-PD-1 immune checkpoint inhibitor therapy model, it was verified that supplementation of NAD+ significantly enhanced the tumor-killing effect of T cells. The researchers found that in the anti-CD19 CAR-T treatment model, almost all mice in the CAR-T treatment group supplemented with NAD+ achieved tumor clearance, while the CAR-T treatment group without NAD+ supplemented only about 20 % Of mice achieved tumor clearance. Consistent with this, in the anti-PD-1 immune checkpoint inhibitor treatment model, B16F10 tumors are relatively tolerant to anti-PD-1 treatment, and the inhibitory effect is not significant. However, the growth of B16F10 tumors in the anti-PD-1 and NAD+ treatment group could be significantly inhibited. Based on this, NAD+ supplementation can enhance the anti-tumor effect of T cell-based immunotherapy. 4.How to supplement NAD+ The NAD+ molecule is large and cannot be directly absorbed and utilized by the human body. The NAD+ directly ingested orally is mainly hydrolyzed by brush border cells in the small intestine. In terms of thinking, there is indeed another way to supplement NAD+, which is to find a way to supplement a certain substance so that it can synthesize NAD+ autonomously in the human body. There are three ways to synthesize NAD+ in the human body: Preiss-Handler pathway, de novo synthesis pathway and salvage synthesis pathway. Although the three ways can synthesize NAD+, there is also a primary and secondary distinction. Among them, the NAD+ produced by the first two synthetic pathways only accounts for about 15% of the total human NAD+, and the remaining 85% is achieved through the way of remedial synthesis. In other words, the salvage synthesis pathway is the key to the human body to supplement NAD+. Among the precursors of NAD+, nicotinamide (NAM), NMN and nicotinamide ribose (NR) all synthesize NAD+ through a salvage synthesis pathway, so these three substances have become the body's choice for supplementing NAD+. Although NR itself has no side effects, in the process of NAD+ synthesis, most of it is not directly converted into NMN, but needs to be digested into NAM first, and then participate in the synthesis of NMN, which still cannot escape the limitation of rate-limiting enzymes. Therefore, the ability to supplement NAD+ through oral administration of NR is also limited . As a precursor for supplementing NAD+, NMN not only bypasses the restriction of rate-limiting enzymes, but is also absorbed very quickly in the body and can be directly converted into NAD+. Therefore, it can be used as a direct, rapid and effective method to supplement NAD+. Expert Reviews: Xu Chenqi (Excellence and Innovation Center of Molecular Cell Science, Chinese Academy of Sciences, Immunology Research Expert) Cancer treatment is a problem in the world. The development of immunotherapy has made up for the limitations of traditional cancer treatment and expanded the treatment methods of doctors. Cancer immunotherapy can be divided into immune checkpoint blocking therapy, engineered T cell therapy, tumor vaccine, etc. These treatment methods have played a certain role in the clinical treatment of cancer. At the same time, this also makes the current focus of immunotherapy research on how to further enhance the effect of immunotherapy and expand the beneficiaries of immunotherapy.
Bontac in Boao Health Food Science Conference & Expo(FHE) From 22 to 25 February 2023, the Boao Health Food Science Conference and Expo was successfully held at the permanent venue of the Boao Forum for Asia in Hainan, China. This international conference build an international platform for exchange and cooperation among government, academia, industry, and industry, academia and research, which aims to promote the development of the health food industry through the exchange of scientific information at home and abroad. Bontac performace in FHE The conference gathered several prominent scientists including 10 academicians, over 200 experts and scholars, and invited many popular food enterprises likely Nestle, Pepsi from the United States, Europe, Japan, Australia, New Zealand and other countries. More importantly, exhibition featured a number of high-tech companies that focus on high-tech development of the production of nutritious and healthy food products. As one of the high-tech companies attending the exhibition, Bontac, which has obtained over 160 international patents and is committed to the design of new biosynthetic pathways to explore and mass-produce natural products for food ingredients, was invited to attend the conference and companies vital stake holders to deliver academic views on the technological innovation and healthy development of the food industry. Figure 1: Xinhua Officical Record for Bontac in FHE Bontac Products in FHE Expo Bontac main products starring NMN, rare ginsenosides, NAD, NADH and NADPH were all present at booth C34 in FHE Expo. And that booth C34 attracted lots of exhibitors to consult who communicated with each other upon appearance owing to the obvious striking advantages likely Bontac manufacture technology of whole coenzyme, sustainable supply chain, complete quality system and environment-protection and energy-saving preparation. What’s more, the academician of the Chinese Academy of Engineering and Chairman of FHE, Chen Junshi also visited Bontac booth and highly commend on the Bontac performance and demonstration. Figure 2: Chen Visited Bontac Booth in FHE Bontac recognizes the importance of the upstream of raw material side in biotechnology as the key to product innovation. On the other hand, with the increasingly demand for high-quality food, synthetic biotechnology stands on the point of the potential to provide consumers with greener and healthier food ingredients. Therefore, as far as Bontac is concerned, developing and shaping innovative technology ownership supports to effectively solving the problem of insufficient plant and animal extracts, reducing the environmental burden, and contributing to carbon neutrality and human sustainable development. At present, Bontac has already launched industrialized stevioside and rare ginsenoside which can be utilized in the field of health food. In future, Bontac will set up more product lines for more raw materials with higher purity and better quality as health food ingredients. Bontac honor time in FHE It was great honor for Bontac to win innovative product enterprise award, which identified Bontac long-term commitment to the exploration and innovation of synthetic biology and health technology products. Furthermore, it also reflects the R&D capability and innovation ability of Bontac in the field of synthetic biology, which will surely inspire Bontac to invest more actively in R&D and innovation. Figure 3: Bontac Award in FHE Dr. Qi Zhang, Founder and Chief Scientist of Bontac, delivered a speech entitled Efficient Green Biosynthesis of Ginsenosides, NMN and other Natural Products at the Innovative Technology and Innovative Manufacturing forum, explaining the green safety, wide applicability and innovative value of synthetic biotechnology from the theoretical source. Figure 4: Dr. Zhang in FHE Dr. Zhang demonstrated that Bontac holds up on the technology of biosynthesis of coenzyme preparation for natural products such as ginsenosides, especially rare ginsenosides Rh2 and Rg3. The advantages focuses on breaking through the limitations of raw materials, facilitating industrial scale-up, shorting reaction cycle, milder conditions, green environment and energy saving, but maintains the point of sustainable development. On the 23rd, a roundtable discussion on the "Technology and Investment in the Food Industry". Shu Shangke, Chairman of Bontac, attended the forum on the theme of Technology and Investment in the Food Industry and said that synthetic biotechnology is bringing about a revolution in the food and pharmaceutical fields, pushing these fields to iterate and upgrade. In the food industry, having strong R&D strength, leading technology and abundant patents are important factors for a company to have core competitiveness and investment value. Figure 5: Shu in FHE
Elevating Wellness: BONTAC's NMN Powder Offerings As we delve into the realm of health and wellness, the spotlight shines brightly on NMN powder, a powerful supplement embraced by many for its potential benefits. At BONTAC, we take pride in offering a premium selection of NMN powder formulations designed to support optimal health and vitality. Our commitment to excellence shines through in our dedication to scientific innovation, top-notch technical support, and unwavering focus on quality. Join us on a journey to explore the transformative effects of BONTAC's NMN powder offerings. Exploring BONTAC's NMN Powder Selection BONTAC's NMN powder selection stands out as a cornerstone of our commitment to promoting wellness. We meticulously source and formulate our NMN powder to ensure the highest purity and efficacy, setting a gold standard in the industry. With a focus on quality and potency, BONTAC's NMN powder are designed to support cellular health, energy production, and overall well-being. Whether you require cutting-edge laboratory equipment, innovative research tools, or transformative bio-based materials, BONTAC has you covered. Our extensive product portfolio spans a wide spectrum, including but not limited to genetic engineering tools, biomaterials, diagnostic assays, regenerative medicine solutions, and environmental sustainability innovations. By providing access to these advanced biotechnology products, we empower businesses to stay ahead of the curve and drive progress in their respective fields. Features and Purity of BONTAC's NMN Powder The hallmark of BONTAC's NMN powder offerings lies in their exceptional quality and purity standards. Our products undergo rigorous testing and quality control measures to guarantee maximum effectiveness and safety. Customers trust in the purity and authenticity of BONTAC's NMN powder, knowing that they are investing in products that deliver tangible results and contribute to their wellness journey. Leveraging BONTAC's NMN Powder for Optimal Health Integrating BONTAC's NMN powder into your daily wellness regimen opens doors to a world of health benefits. Our team is dedicated to providing unparalleled technical support and expertise to guide you through the supplementation process. Partnering with BONTAC ensures that you have access to premium NMN formulations backed by scientific research and innovation, empowering you to achieve your health goals with confidence. Conclusion In conclusion, BONTAC's NMN powder offerings represent a commitment to holistic wellness and vitality. With a focus on excellent products, technical innovation, and unwavering customer support, we stand as your trusted partner in the journey toward optimal health. Embrace the power of BONTAC's premium NMN powder and elevate your well-being to new heights.