Company
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Back to Company SearchZYMTRONIX CATALYTIC SYSTEMS, INC.
UEI: J6Y3K7EWJP95
Number of Employees: 21
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
SBIR/STTR Involvement
Year of first award: 2014
5
Phase I Awards
3
Phase II Awards
60%
Conversion Rate
$1,054,297
Phase I Dollars
$5,532,961
Phase II Dollars
$6,587,258
Total Awarded
Awards
Scaling-up flow processes for the chemoenzymatic synthesis of a sialylated glycan
Amount: $2,258,638 Topic: 300
Abstract - Human milk oligosaccharides (HMOs) are abundant components of human milk that hold extraordinary potential as novel formula supplements and therapeutic agents to improve gut inflammatory disorders, autoimmune and allergic diseases. Originally considered prebiotics that help shape the gut microbiome of breastfed infants, some HMOs are increasingly becoming known for their beneficial immunomodulatory and anti-inflammatory properties. HMOs prevent pathogen attachment to infant mucosal surfaces to lower the risk of infections, modulate epithelial and immune cell responses, reduce excessive mucosal leukocyte infiltration and activation, and lower the risk of necrotizing enterocolitis. However, the inability to source pure, structurally defined complex HMOs in sufficient quantities has hindered their systematic study and efforts to leverage the extraordinary biomedical potential of these commercially relevant human milk bioactives. In response to the critical need to significantly improve the production efficiency of HMOs, Zymtronix is applying its proprietary multienzyme immobilization technology to produce most HMO milk constituents via cell-free biomanufacturing, thereby removing a major barrier to their investigation in the infant and adult therapeutic space—a mission aligned with the Glycoscience NIH Common Fund. In Phase I, Zymtronix demonstrated successful production of multiple HMOs. In this Phase II project, Zymtronix proposes to significantly improve the production efficiency of human milk oligosaccharides (HMOs), initially focusing on a sialylated HMO which has been demonstrated to be highly protective against necrotizing enterocolitis (NEC) – a devastating inflammatory gastrointestinal disorder with a 10-50% mortality rate in premature infants and total annual cost burdens upwards of $1B. To validate the quality and efficacy of this compound in small and large animal models of NEC, Zymtronix is partnering with Drs. Lars Bode (UCSD) and Doug Burrin (Baylor College of Medicine), world-class experts in HMOs, pediatric nutrition, and gastroenterology. Phase II Aims are to optimize biocatalytic production (Aim 1), conduct a proof-of-concept study to replicate efficacy study in rats (Aim 2), demonstrate a scalable production and purification method (Aim 3), and for the first time, demonstrate the use of this sialylated HMO at multi-gram scale in piglets (Aim 4). The project will establish a cost-effective and industrially scalable method of production that will put 100s grams quantities into the hands of researchers and commercial partners who desire to systematically investigate its efficacy against NEC with the long-term goal of substantially improving the outcome for neonates at risk of NEC. This HMO is just one of several beneficial molecules that will be substantially more accessible as an outcome of the proposed work, creating the ability to utilize these free glycans in a wide range of applications from nutrition to therapeutics.
Tagged as:
SBIR
Phase II
2024
HHS
NIH
Multi-gram enzymatic production of complex glycans by flow processes
Amount: $2,527,145 Topic: 300
Abstract: Zymtronix proposes to significantly improve production efficiency of glycans via new flow processes based on chemoenzymatic catalysis to take significant steps towards broader commercial access. The first glycans of interest are human milk oligosaccharides (HMOs), which have large commercial relevance in infant nutrition, disease prevention and therapeutics. The primary hurdle towards the broader application of complex synthetic glycans in research, preclinical and commercial applications is their affordability. The goal of the proposed research is to lower the production costs of large and complex HMOs (rt5 DP) by continuous flow processes where each step of synthesis is conducted in modules. Zymtronix's technology enables (i) high enzyme activity and stability ensuring the reuse of enzyme and (ii) enables the co-immobilization of multiple enzymes to incorporate enzymatic recycling for sub-stoichiometric use of reagents to impart significant cost- reductions. For this fast-track, we will produce large human milk oligosaccharides (HMOs), the third largest component of breast milk that are particularly commercially relevant glycan models. While some simple probiotic HMOs can be effectively produced via fermentation for infant formula (2'FL, 3 DP), complex and branched HMOs are elusive and have been marginally produced at high cost via chemoenzymatic catalysis. Zymtronix's technology solution will significantly improve production of glycans, starting with HMOs, while imparting significant cost savings. Fast-track Phase I specific aims are to immobilize 6 enzymes and to combine them in a defined sequence to generate sialylated lacto-N-neopentaoses. (I) Aim 1: Immobilize 6 individual enzymes on sintered beads using ZymTrap3D technology. 4 transferases and 2 activated-sugar-producing enzymes for in-situ synthesis of GlcNAc-UDP, Gal-UDP and Neu5Ac-CMP, (II) Aim 2: Demonstrate sequential, modular synthesis of 1 mg of α- 2,3- and α-2,6-sialyl lacto-N-pentaoses on beads. (III) Aim 3: Produce 100 mg of α-2,3-sialyl lacto-N- neopentaose using a flow cell. Fast-track Phase II aims are to scale up production of three linear fucosyl- and sialyl-lacto-N-neopentaoses from Aim1. (I) Aim 1: Development of HMO fucosylation and branching modules towards the 100 mg production of 6 biantennary lacto-N-neohexaoses and heptaoses. The modularity of branching followed by three possible `functionalization' modules, and a final elongation step allows the production of 6 biantennary HMOs. (II) Aim 2: Development of flow cells with in situ reagent recycling for multi-gram scale HMO production. Production and cost metrics will be assessed. (III) Aim 3: Scaling up engineering and production of 10 g and then 100 g of fucosyl- and sialyl-lacto-N-neopentaoses. Work will include in-house enzyme production and HPLC purification of HMOs.
Tagged as:
SBIR
Phase II
2022
HHS
NIH
Multi-gram enzymatic production of complex glycans by flow processes
Amount: $354,457 Topic: 300
Abstract: Zymtronix proposes to significantly improve production efficiency of glycans via new flow processes based on chemoenzymatic catalysis to take significant steps towards broader commercial access. The first glycans of interest are human milk oligosaccharides (HMOs), which have large commercial relevance in infant nutrition, disease prevention and therapeutics. The primary hurdle towards the broader application of complex synthetic glycans in research, preclinical and commercial applications is their affordability. The goal of the proposed research is to lower the production costs of large and complex HMOs (andgt;5 DP) by continuous flow processes where each step of synthesis is conducted in modules. Zymtronixandapos;s technology enables (i) high enzyme activity and stability ensuring the reuse of enzyme and (ii) enables the co-immobilization of multiple enzymes to incorporate enzymatic recycling for sub-stoichiometric use of reagents to impart significant cost- reductions. For this fast-track, we will produce large human milk oligosaccharides (HMOs), the third largest component of breast milk that are particularly commercially relevant glycan models. While some simple probiotic HMOs can be effectively produced via fermentation for infant formula (2andapos;FL, 3 DP), complex and branched HMOs are elusive and have been marginally produced at high cost via chemoenzymatic catalysis. Zymtronixandapos;s technology solution will significantly improve production of glycans, starting with HMOs, while imparting significant cost savings. Fast-track Phase I specific aims are to immobilize 6 enzymes and to combine them in a defined sequence to generate sialylated lacto-N-neopentaoses. (I) Aim 1: Immobilize 6 individual enzymes on sintered beads using ZymTrap3D technology. 4 transferases and 2 activated-sugar-producing enzymes for in-situ synthesis of GlcNAc-UDP, Gal-UDP and Neu5Ac-CMP, (II) Aim 2: Demonstrate sequential, modular synthesis of 1 mg of α- 2,3- and α-2,6-sialyl lacto-N-pentaoses on beads. (III) Aim 3: Produce 100 mg of α-2,3-sialyl lacto-N- neopentaose using a flow cell. Fast-track Phase II aims are to scale up production of three linear fucosyl- and sialyl-lacto-N-neopentaoses from Aim1. (I) Aim 1: Development of HMO fucosylation and branching modules towards the 100 mg production of 6 biantennary lacto-N-neohexaoses and heptaoses. The modularity of branching followed by three possible `functionalizationandapos; modules, and a final elongation step allows the production of 6 biantennary HMOs. (II) Aim 2: Development of flow cells with in situ reagent recycling for multi-gram scale HMO production. Production and cost metrics will be assessed. (III) Aim 3: Scaling up engineering and production of 10 g and then 100 g of fucosyl- and sialyl-lacto-N-neopentaoses. Work will include in-house enzyme production and HPLC purification of HMOs.PUBLIC HEALTH RELEVANCE: Glycans are complex and highly diverse carbohydrates that are the predominant molecules on the cell surface or in human milk and serve as the first point of contact between cells, the extracellular matrix and pathogens. While their role as mediators of cellular interaction is still poorly understood, it is crucial to improve the accessibility and affordability of these molecules for clinical evaluations and commercial distribution. Zymtronix is developing novel modular methods and processes for increased scale of production at greatly reduced costs of defined glycans starting with complex Human Milk Oligosaccharides (HMOs) potentially allowing for the development of improved infant formulas and bioactive glycosylated molecules.
Tagged as:
SBIR
Phase I
2020
HHS
NIH
A high-throughput cell-free profiling platform integrating high metabolic diversity for chemical safety assessment
Amount: $224,930 Topic: NIEHS
Abstract Roughlynew drugs and chemicals are commercialized each year successfully clearing research and developmentRandamp Dhurdles to meet the safety requirements of regulators such as the U SFood and Drug AdministrationThese successeshoweverare the exception rather than the rule making it advantageous for Randamp D programs to have methods in place that ensure unsafe compoundsfail fastwell before entering time and resource intensive animal or human testingIn vitro toxicity assays have assumed this early screening role but lack the ability to assess the contribution of potentially toxic metabolites that the body produces from otherwise safe parent chemicalsThe integration of metabolic profiling into current toxicity screening platforms is therefore crucial to chemical riskexposureand drug safety assessmentsThe cytochrome PCYPfamily is one of the most important families of enzymes involved in human metabolismmetabolizing aboutof all xenobiotics and drugs in the liverIntegrating the function of CYPs and other metabolic familiese gUGTsin drug metabolism and pharmacokineticsDMPKare key to increasing the safety of drugs as well as speeding their developmentCurrent approaches used by pharmaceutical companies and contract research organizations rely on cultured hepatocyteswhich co activate multiple enzymatic pathways in a single integrated platformAlthough this method mimics liver physiologythere are several drawbacks including limited incubation time and metabolite productionthe need to statistically evaluate significant background metabolomesand complex quality control challenges inherent in cell handling techniquesZymtronix has developed a novelcell free technology that offers increased metabolite productionenzyme specific metabolomes with little backgroundand improved quality control compared to cell based systemsallowing for reduced cost and ease of useThis Phase I project will generate a proof of concept product for a Toxcompatiblehigh throughputHTPmetabolic processing unit built on a proprietary enzyme anchoring technologyFirstwe will adapt our existing technology to a functionalizedwell microplate lidand then optimize and characterize the newly engineered scaffold using CYP ACYP Band UGT Amodel enzymesFinallywe will use liquid chromatography mass spectrometry analysis to demonstrate the conversion of six model compounds by the enzyme trioindividually and in combinationand compare the metabolome with that produced by pooled human liver microsomesThe project will prepare us for future Phase II researchin which we will explore a larger number of chemical substrates with an expanded set of CYPs UGTs to determine a critical set of metabolic enzymes that produce a diverse and physiologically relevant metabolomeThe product will be constructed inwell microplate format to facilitate HTP robotic handling and integration with downstream cell based assays Narrative Because metabolism significantly affects the toxicity of chemicals taken up by the bodydetermining the metabolic profile of xenobioticsincluding commercial chemicalsfood ingredients and pharmaceuticalsis a critical part of chemical riskexposureand drug safety assessmentsCurrently proposed cell based assay systems for evaluating the environmental health impact of metabolites are labor intensivecostly and pose challenges to quality control and analysisZymtronix is developing a tunable cell free toxicity screening product for the ADME market that is Toxcompatible with a proprietary enzyme immobilization technology that will offer improved quality controlreduced costand ease of use
Tagged as:
SBIR
Phase I
2019
HHS
NIH
Flow processes for the chemoenzymatic synthesis of fucosylated and sialylated glycans
Amount: $224,987 Topic: 300
Project Summary Abstract Zymtronix is developing a series of highly tunable materials and processes for universal enzyme immobilization based on hierarchical magnetic metamaterialsThis enzyme immobilization platform is being designed to quickly find the optimal conditions to immobilize single and full systems of enzymesIt affords enzyme stabilitymaximal use of substratesincluding co factorsand recent developments imparts modularity for flow processesFor this phase I projectZymtronix proposes to develop its technology to improve the efficiency of defined glycan productionfocusing on human milk oligosaccharidesHMOswith optimized full enzyme systems immobilized on macroporous scaffolds specifically designed for continuous flow processingLibraries of large and complex glycans have been made availablethanks to NIH s Common Fund programAccelerating Translation of GlycoscienceIntegration and Accessibilitylaunched inCurrentlythe primary hurdle towards the broader application of complex synthetic glycans in researchpreclinical and commercial applications is their availability and affordabilityZymtronix s technology allows maintaining high activities and co immobilizing multiple enzymes to mimic live cell reactions and combined in situ production of active sugarstransfer of the sugar for de novo synthesiswhile ensuring the reuse of the enzymes and substoichiometric use of cofactors for significant cost reductionFor this Phase I we will demonstrate key steps for the production of Human milk oligosaccharidesHMOsthe third largest component of breast milk that are particularly commercially relevant glycan modelsWhile some simple probiotic HMOs can be effectively produced via fermentation for infant formulaFLDPcomplex and branched prophylactic HMOs are elusive and have been marginally produced at high cost via chemocatalysisZymtronix s technology solution will significantly improve HMO production efficiency while imparting significant cost savingsThe Phase I proofof concept will primarily focus onkey steps of glycan functionalization with fucose and sialic acid activation and transfer onto HMO backbones with immobilized enzymesSpecific Aims for this Phase I project includeProduce two key activated sugars CMP Sialic acid and GDP L fucose with immobilized enzymesPerform the fucosylation and siallyation of lactose and lactose N tetraose with immobilized enzymesDemonstrate fucosylation of Lactose directly with L fucose with an immobilized three enzyme system including GTP recyclingFor Phase IIwe proposed to expand our continuous flow approach for gram scale synthesis of a glycan libraryandgtDPconsisting oflinearbiantennaryandtriantennary HMOs and go beyond HMOs with glycosylation of active small molecules Project Narrative Glycans are complex carbohydrate structures that are the predominant molecules on the cell surface or in milk and serve as the first point of contact between cellsthe extracellular matrix and pathogensWhile their role as mediators of cellular interaction is still poorly understoodit is crucial to improve the accessibility and affordability of these moleculesZymtronixnovel modular method and processes for producing complex HMOsand other defined glycanswill enhance production efficiency of complex carbohydrates while lowering costspotentially allowing for development of improved infant formulas and other bioactive glycosylated molecules
Tagged as:
SBIR
Phase I
2019
HHS
NIH
A seed-coating mixed enzyme formula for the control of fungal and bacterial pathogens
Amount: $99,923 Topic: 8.2
This project seeks to improve food security through the development of a novel crop disease management tool. Modern agriculture relies on the heavy use of pesticides to control plant diseases and protect crops from significant losses, and many of the most important disease control products are quickly losing efficacy due to resistance development. Consequences of pesticide use include potentially negative effects on human health and the environment and selection for pesticide resistance, and the increased use of pesticides since 1960 has not resulted in a significant decrease in crop losses. Novel crop protection solutions will ensure crops are protected against diseases amid global trade and a changing climate which threaten to introduce or increase the severity of diseases in areas where they were previously insignificant. More sustainable practices are needed to protect arable lands from deterioration against the backdrop of intensive agricultural production as well as to protect effective pesticides from becoming obsolete through the selection of resistant pests and pathogens. From 2001 through 2003, actual crop loss in eleven major crops (including tomato) due to pathogens was estimated at 68% of the theoretical potential loss, compared to 61% and 26% for animal pests and weeds, respectively. This indicates a significant opportunity to improve the efficiency of plant disease management. The goal of this project is to provide seed producers with a novel and sustainable seed coating technology which will increase crop yields and food production by protecting seeds and seedlings against a diversity of diseases, and by protecting the longevity of important antimicrobials by reducing the rate of resistance development.Coating seeds with antimicrobials, mostly fungicides, to protect against disease has been practiced for centuries, and remains one of the most efficient ways of ensuring that seedlings are protected from soilborne and seedborne pathogens. Early seed coating technologies included the use of arsenic, mercury and copper, but concerns over acute toxicity, mishandling accidents such as the mass poisoning by methylmercury of 1971 in Iraq, and environmental impacts have given rise to more targeted, or site-specific, compounds. A drawback to site-specific products is an increased likelihood of resistance development compared to multi-site compounds, due to the fact that a single mutation can confer resistance. Zymtronix has developed a solution to this problem through the use of its enzyme immobilization system, which uses stabilized antimicrobial enzymes delivered as a seed coating to protect against a broad spectrum of plant pathogens. Zymtronix's enzyme system relies on the production of non-site-specific free radicals and reactive oxygen species, thereby reducing the likelihood of resistance development. Additionally, we have demonstrated compatibility with a commercial fungicide and antibiotic and shown potential for reducing pesticide application rates and reducing the probability of resistance development without compromising control. This novel method will reduce reliance on existing agrochemicals like fungicides and antibiotics, thereby decreasing the likelihood of resistance development while simultaneously providing an alternative, effective method for managing a broad spectrum of major crop diseases.For this Phase I project, we are initially targeting the devastating tomato seedling disease damping-off, which can affect nearly all crops, as well bacterial speck, an important bacterial disease of tomato that can serve as a model for many other seed-borne and soil-borne bacterial plant diseases. We will determine the efficacy of, and potential synergy between, our stabilized enzyme formula and several commercial fungicides and antibiotics in laboratory tests. We will then use that information to develop several unique seed-coating formulas. Tomato seeds treated with those formulas will be exposed to dampi
Tagged as:
SBIR
Phase I
2017
USDA
SBIR Phase II: Enzyme-based Magnetic Catalysts for Active Pharmaceutical Intermediates (APIs) Manufacturing
Amount: $747,178 Topic: BC
The broader commercial potential of this Small Business Innovation Research Phase II project is the commercial development of novel materials and processes for the immobilization of enzymes. The project is targeting enzymes as catalysts to be used in the manufacturing of active pharmaceutical intermediates (API). The use of enzyme for the production of pharmaceuticals has the potential to reduce cost, complexity and improve efficiency in making these products. The green, cost-efficient and scalable oxidative immobilized enzymes will benefit manufacturers by improving their production efficiencies and economics as well as minimizing adverse environmental impact. The technology could make benign oxidative enzymes commercially competitive replacing expensive precious metal catalysts, toxic, or other hazardous chemicals used in the production processes for APIs. The industrial applications for this technology could be broad well beyond the pharmaceutical arena. The technical objectives of this Phase II research project are to (1) develop oxidative enzyme constructs and biocatalytic schemes for the production of high-value commercial active pharmaceutical ingredients (APIs), (2) develop and produce magnetic macroporous scaffolds, and (3) improve operation of commercial reactors for continuous flow manufacturing or retrofit existing production processes using these magnetic catalysts with immobilized enzymes. This project enables immobilization to become a part of the selection process: enzymes can be selected for their true potential in their immobilized form by engineering enzyme immobilization with three levels of innovation: entrap commercially-available or third-party engineered enzymes into magnetic nanoclusters; create high-surface area scaffolds that stabilize the magnetic nanocluster assemblies, providing cost and process advantages of maintaining the nanocluster assemblies in suspension magnetically. This project is focusing on a high-potential, well-described and commercially available enzyme from the oxidoreductase family that will be used the synthesis of drug intermediates by enzyme-producers and enzyme-end users in the pharmaceutical sector.
Tagged as:
SBIR
Phase II
2015
NSF
SBIR Phase I: A green enzyme-based oxidative platform for fine chemical synthesis and remediation applications
Amount: $150,000 Topic: BC
This Small Business Innovation Research Phase I project aims to increase the effectiveness of oxidative enzymes of high potential in chemical synthesis and chemical remediation applications. Enzyme-based systems, the greenest and most energy efficient processes known to-date, are replacing chemical-based systems due to their superior potential for energy savings and environmental benefits. While at the forefront of the green chemistry revolution, however, enzyme-based systems are difficult to come by. Their adoption has not been as fast, as widespread, or as beneficial as it otherwise could be because oxidative enzymes are not cost effective enough to replace chemicals. This project is developing an integrated technology for oxidative enzymes for industrial use. The project objectives consist of (1) manufacturing continuous flow reactors dedicated to processing ZYMtronix?s catalysts, (2) developing a synthesis process for key pharmaceutical precursors used in cancer treatment, and (3) demonstrating the remediation application for industrial contaminants. The anticipated technical results will benchmark reactor characteristics and the catalytic metrics of the aforementioned processes. The broader commercial potential of this project is to facilitate the adoption of oxidative enzymes in synthesis and remediation applications because they can replace precious metal catalysts, toxic solvents, and energy intensive processes. Additional benefits translate to safer processes and products for manufacturers, consumers and the environment. ZYMtronix patent-pending technology is estimated to be substantially more efficient and cost effective to operate when compared with chemical systems, increasing enzyme activity, decreasing enzyme inhibition, and expanding the enzyme´s range of operable conditions. Combined with proprietary reactors being developed, the catalysts can be recycled for continuous use. ZYMtronix´s technology serves the fine chemicals, pharmaceutical, as well as the water remediation, markets applicable to oxidative enzyme processes.
Tagged as:
SBIR
Phase I
2014
NSF