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Patent
Givaudan and Manus Biosynthesis, Inc. | Date: 2017-06-28

The present disclosure relates to methods for producing oxygenated terpenoids, and preparation of compositions and formulations thereof. Polynucleotides, derivative enzymes, and host cells for use in such methods are also provided.


Patent
Manus Biosynthesis, Inc. | Date: 2017-06-28

The present invention relates to methods for producing oxygenated terpenoids. Polynucleotides, derivative enzymes, and host cells for use in such methods are also provided.


Grant
Agency: NSF | Branch: Standard Grant | Program: | Phase: SMALL BUSINESS PHASE I | Award Amount: 225.00K | Year: 2016

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) project will be to reduce the incidence of Lyme Disease through the biomanufacturing of a novel natural acaricide. New cases of Lyme Disease have grown by nearly 50% over the past decade while the existing synthetic acaricides are dwindling in use due to regulatory and consumer safety concerns. The CDC and USDA have begun to champion a highly effective natural acaricide extracted from grapefruit. This target molecule is a GRAS-approved natural product, which has been used extensively as a food ingredient for decades. It is thought that this compelling safety benefit combined with potent efficacy will spur increased spraying in public areas and private residences. However, the cost of producing this natural acaricide has been prohibitive, and there is an opportunity to develop alternative sustainable production technologies.

This SBIR Phase I project proposes to develop a microbial process for the economical and sustainable production of a highly potent natural acaricide. Increasing wariness of synthetic insecticides combined with the need to prevent tick-borne illnesses creates a tremendous opportunity for natural acaricides. The projects terpene target has long been known as a highly effective acaricide; however, its commercialization has been hampered by a high cost of production. The aim is to develop an alternative fermentation process for biosynthetic production enabling the cost reductions required to effectively penetrate the acaricide market. The main objective for this project is to increase titers by an order of magnitude. This will be accomplished by employing established and novel metabolic and protein engineering approaches. Overall, this project will provide a new sustainable, cost-effective production route, thereby enabling acaricide commercialization.


Grant
Agency: National Science Foundation | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 150.00K | Year: 2013

This Small Business Innovation Research Phase I project will develop a custom-designed microbial biocatalyst for the renewable production of high value terpenoid biochemicals. Terpenoid biochemicals derived from essential oils are used in numerous consumer products and as food additives. Many of them accumulate in nature in various stereo-isomeric forms, each of which possesses unique properties and applications. These molecules are believed to function principally in ecological roles, serving as herbivore-feeding deterrents, antifungal defenses, and pollinator attractants. The research objective is to develop a fermentation process for biosynthetic production allowing increased adoption of such natural alternatives to synthetic chemicals. Multivariate-Modular Metabolic engineering (MMME) approaches will be used to transfer the natural biosynthetic pathway from the plant to a bacterial host and to optimize the metabolic flux for the overproduction at a commercially viable level. A high-productivity strain is anticipated, suitable for continued commercialization efforts. Overall, this project, if successful, will provide a new sustainable production route for these natural chemicals. The broader impact/commercial potential of this project is the development of a microbial process for the economic and sustainable production of high value terpenoid biochemicals. These terpenoid biochemicals have applications in a variety of industries ranging from agro-chemicals, petro-chemicals and flavor and fragrance (F & F) chemicals; specifically they are commonly used as flavor agents, bio- herbicides, sprout inhibitors and as bio-pest repellents. In all, the total potential addressable markets exceed $3 Billion. Microbial production will benefit society by improving the renewability of the production process and by relocating production from overseas to the US. In summary, the development of microbes capable of producing the target will enable sustainable production of the target as well as create jobs in the US. This research will develop generalizable microbial strain engineering techniques for the high-volume production of natural products through a sustainable manufacturing process.


Grant
Agency: National Science Foundation | Branch: | Program: STTR | Phase: Phase I | Award Amount: 225.00K | Year: 2013

This Small Business Innovation Research (STTR) Phase I project aims to develop a novel, high flux terpenoid precursor pathway by circumventing limitations of the bacterial methyl erythritol-phosphate (MEP) pathway for the renewable production of monoterpenoids. Monoterpenoids are natural chemical precursors for several consumer products, and many are produced via highly polluting chemical processes. In the proposed project the plan is to sidestep some of the MEP pathway limitations by designing de novo metabolic pathways. The designed/predicted enzymes will be characterized individually and assembled into a pathway. Further, multivariate-modular metabolic engineering (MMME) approaches will be used to assemble the upstream and downstream pathways to optimize the metabolic flux for the overproduction at commercially viable levels. The broader impact/commercial potential of this project, if successful, will be to develop a microbial monoterpenoid production platform from renewable sugars that will retain and develop sustainable manufacturing of monoterpenoid-derived products in the US. By this strategy, terpenoids can be made at much higher productivities than the native bacterial MEP pathway. While the immediate focus is on the $1B+ monoterpene/derivative market, this approach will benefit US manufacturing of all terpenoids, in total a $5B+ market. Overall, this project will provide a new sustainable production route for these natural chemicals.


Grant
Agency: NSF | Branch: Standard Grant | Program: | Phase: STTR PHASE I | Award Amount: 225.00K | Year: 2013

This Small Business Innovation Research (STTR) Phase I project aims to develop a novel, high flux terpenoid precursor pathway by circumventing limitations of the bacterial methyl erythritol-phosphate (MEP) pathway for the renewable production of monoterpenoids. Monoterpenoids are natural chemical precursors for several consumer products, and many are produced via highly polluting chemical processes. In the proposed project the plan is to sidestep some of the MEP pathway limitations by designing de novo metabolic pathways. The designed/predicted enzymes will be characterized individually and assembled into a pathway. Further, multivariate-modular metabolic engineering (MMME) approaches will be used to assemble the upstream and downstream pathways to optimize the metabolic flux for the overproduction at commercially viable levels.

The broader impact/commercial potential of this project, if successful, will be to develop a microbial monoterpenoid production platform from renewable sugars that will retain and develop sustainable manufacturing of monoterpenoid-derived products in the US. By this strategy, terpenoids can be made at much higher productivities than the native bacterial MEP pathway. While the immediate focus is on the $1B+ monoterpene/derivative market, this approach will benefit US manufacturing of all terpenoids, in total a $5B+ market. Overall, this project will provide a new sustainable production route for these natural chemicals.


Grant
Agency: National Science Foundation | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 150.00K | Year: 2012

This Small Business Innovation Research (SBIR) Phase I project will address the potential of synthetic biology and metabolic engineering technologies to generate microbial strains over-producing a non-caloric natural sweetener. Current production and utilization of natural sweeteners is limited due to the high cost of the cultivation and production from native plant sources. So, although natural sweeteners have been used for thousands of years, and are known for their healthy and non-caloric properties, their high production cost prevents them from directly competing with synthetic sweeteners extensively used in beverages and carbonated soft drinks. Our objective is to develop a fermentation process for biosynthetic production allowing increased adoption of low-calorie, natural sweeteners in consumer markets. Metabolic engineering approaches will be used to transfer the natural biosynthetic pathway from the plant to a bacterial host and optimize the metabolic flux for the overproduction at a commercially viable level. We anticipate that a high-productivity strain will be obtained, suitable for continued commercialization efforts. Overall, this project, if successful, will provide a new sustainable production route to the non-caloric natural sweeteners. The broader impact/commercial potential of this project is the development of a microbial process for the economical and sustainable production of non-caloric natural sweetener, with a potential $3 billion global market. The use of this sweetener will improve taste profiles and expand adoption of low-calorie beverages, confectionaries, baked goods, dairy products, and so on, thus benefitting public health by reducing incidence of diabetes and other obesity-related diseases. Such benefits will translate to reduced healthcare cost both in the U.S. and globally. Additionally, this research will develop generalizable synthetic biology techniques for the high-volume production of natural products with many applications for human health and wellness.


Grant
Agency: NSF | Branch: Standard Grant | Program: | Phase: SMALL BUSINESS PHASE I | Award Amount: 180.00K | Year: 2012

This Small Business Innovation Research (SBIR) Phase I project will address the potential of synthetic biology and metabolic engineering technologies to generate microbial strains over-producing a non-caloric natural sweetener. Current production and utilization of natural sweeteners is limited due to the high cost of the cultivation and production from native plant sources. So, although natural sweeteners have been used for thousands of years, and are known for their healthy and non-caloric properties, their high production cost prevents them from directly competing with synthetic sweeteners extensively used in beverages and carbonated soft drinks. Our objective is to develop a fermentation process for biosynthetic production allowing increased adoption of low-calorie, natural sweeteners in consumer markets. Metabolic engineering approaches will be used to transfer the natural biosynthetic pathway from the plant to a bacterial host and optimize the metabolic flux for the overproduction at a commercially viable level. We anticipate that a high-productivity strain will be obtained, suitable for continued commercialization efforts. Overall, this project, if successful, will provide a new sustainable production route to the non-caloric natural sweeteners.

The broader impact/commercial potential of this project is the development of a microbial process for the economical and sustainable production of non-caloric natural sweetener, with a potential $3 billion global market. The use of this sweetener will improve taste profiles and expand adoption of low-calorie beverages, confectionaries, baked goods, dairy products, and so on, thus benefitting public health by reducing incidence of diabetes and other obesity-related diseases. Such benefits will translate to reduced healthcare cost both in the U.S. and globally. Additionally, this research will develop generalizable synthetic biology techniques for the high-volume production of natural products with many applications for human health and wellness.


Grant
Agency: National Science Foundation | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 225.00K | Year: 2016

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) project will be to reduce the incidence of Lyme Disease through the biomanufacturing of a novel natural acaricide. New cases of Lyme Disease have grown by nearly 50% over the past decade while the existing synthetic acaricides are dwindling in use due to regulatory and consumer safety concerns. The CDC and USDA have begun to champion a highly effective natural acaricide extracted from grapefruit. This target molecule is a GRAS-approved natural product, which has been used extensively as a food ingredient for decades. It is thought that this compelling safety benefit combined with potent efficacy will spur increased spraying in public areas and private residences. However, the cost of producing this natural acaricide has been prohibitive, and there is an opportunity to develop alternative sustainable production technologies. This SBIR Phase I project proposes to develop a microbial process for the economical and sustainable production of a highly potent natural acaricide. Increasing wariness of synthetic insecticides combined with the need to prevent tick-borne illnesses creates a tremendous opportunity for natural acaricides. The project's terpene target has long been known as a highly effective acaricide; however, its commercialization has been hampered by a high cost of production. The aim is to develop an alternative fermentation process for biosynthetic production enabling the cost reductions required to effectively penetrate the acaricide market. The main objective for this project is to increase titers by an order of magnitude. This will be accomplished by employing established and novel metabolic and protein engineering approaches. Overall, this project will provide a new sustainable, cost-effective production route, thereby enabling acaricide commercialization.


Grant
Agency: NSF | Branch: Standard Grant | Program: | Phase: SMALL BUSINESS PHASE I | Award Amount: 150.00K | Year: 2013

This Small Business Innovation Research Phase I project will develop a custom-designed microbial biocatalyst for the renewable production of high value terpenoid biochemicals. Terpenoid biochemicals derived from essential oils are used in numerous consumer products and as food additives. Many of them accumulate in nature in various stereo-isomeric forms, each of which possesses unique properties and applications. These molecules are believed to function principally in ecological roles, serving as herbivore-feeding deterrents, antifungal defenses, and pollinator attractants. The research objective is to develop a fermentation process for biosynthetic production allowing increased adoption of such natural alternatives to synthetic chemicals. Multivariate-Modular Metabolic engineering (MMME) approaches will be used to transfer the natural biosynthetic pathway from the plant to a bacterial host and to optimize the metabolic flux for the overproduction at a commercially viable level. A high-productivity strain is anticipated, suitable for continued commercialization efforts. Overall, this project, if successful, will provide a new sustainable production route for these natural chemicals.

The broader impact/commercial potential of this project is the development of a microbial process for the economic and sustainable production of high value terpenoid biochemicals. These terpenoid biochemicals have applications in a variety of industries ranging from agro-chemicals, petro-chemicals and flavor and fragrance (F&F) chemicals; specifically they are commonly used as flavor agents, bio- herbicides, sprout inhibitors and as bio-pest repellents. In all, the total potential addressable markets exceed $3 Billion. Microbial production will benefit society by improving the renewability of the production process and by relocating production from overseas to the US. In summary, the development of microbes capable of producing the target will enable sustainable production of the target as well as create jobs in the US. This research will develop generalizable microbial strain engineering techniques for the high-volume production of natural products through a sustainable manufacturing process.

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