Use of galacturonate and or galacturonate polymers in conjunction with carbohydrates to control metabolic state of organisms
Inventors
Zu, Theresah N. K. • Sund, Christian J. • Liu, Sanchao • Gerlach, Elliot S.
Assignees
United States Department of the Army
Publication Number
US-12241111-B2
Publication Date
2025-03-04
Expiration Date
2039-05-21
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Abstract
A method of producing chemicals includes providing fermentative cells; co-feeding any of galacturonate and galacturonate polymers with carbohydrates to the fermentative cells; and producing a chemical from the fermentative cells. The fermentative cells may include any of Clostridium acetobutylicum and Clostridium saccharoperbutylacetonicum. The carbohydrates may include any of glucose, mannose, galactose, fructose, arabinose, xylose, sucrose, lactose, maltose, cellobiose, and starch. The method may include providing a substantially equal proportion of the any of galacturonate and galacturonate polymers and the carbohydrates for co-feeding to the fermentative cells. The method may include altering a proportion of the any of galacturonate and galacturonate polymers to the carbohydrates. The method may include modulating a production of the chemical by altering the proportion of the any of galacturonate and galacturonate polymers to the carbohydrates. The chemical may include any of acetate and butyrate.
Core Innovation
The invention provides a method of producing chemicals by co-feeding fermentative cells with any of galacturonate and galacturonate polymers together with carbohydrates. This co-feeding allows modulation of the metabolic state of anaerobic organisms by controlling the regeneration of reduced electron carriers, thereby influencing chemical production using organisms having natural or synthetic pathways.
The method includes providing fermentative cells such as Clostridium acetobutylicum or Clostridium saccharoperbutylacetonicum, and co-feeding them with mixtures of galacturonate (or its polymers) and carbohydrates such as glucose, mannose, galactose, fructose, arabinose, xylose, sucrose, lactose, maltose, cellobiose, and starch. Changing the ratio of these co-fed substrates fine-tunes the production of desired chemicals, including acetate and butyrate, by modulating the intracellular redox environment via controlled production of reduced cofactors like NADH and NADPH.
The problem being addressed arises from limitations in traditional fermentation processes that focus primarily on improving product yields without adequately controlling the metabolic and redox state of fermentative organisms. Conventional methods are often inflexible, requiring metabolic engineering for pathway modifications, and are unable to handle complex feedstocks effectively. Moreover, glucose is conventionally considered a preferred substrate, inhibiting utilization of alternative substrates. This invention overcomes these issues by demonstrating that co-feeding galacturonate and carbohydrates enables co-utilization without genetic modifications, providing a flexible and fine-tunable metabolic control mechanism for optimizing chemical production.
Claims Coverage
The patent includes two independent claims detailing methods for controlling metabolic and fermentation processes by co-feeding substrates of different oxidation states to anaerobic organisms and fermentative organisms.
Controlling metabolic process through co-feeding substrates of different oxidation states
A method of controlling a metabolic process by providing an anaerobic organism and co-feeding it with a first chemical substrate and a second chemical substrate with different oxidation states at a predetermined mixture ratio to primarily produce a first chemical. The method involves controlling regeneration of reduced electron carriers by altering the ratio of the substrates, and sequentially co-feeding altered mixture ratios to produce a second chemical.
Controlling fermentation process by adjusting feedstock ratios
A method of controlling a fermentation process by providing a fermentative organism and co-feeding it with a mixture of at least two feedstock materials at a first ratio to primarily produce a first chemical. The method includes altering the ratio to a second ratio, and sequentially co-feeding the organism with the altered mixture to primarily produce a second chemical. The fermentative organism co-utilizes the feedstocks to varying degrees, using oxidative states of the substrates to modulate production of chemicals such as lactate, acetoin, acetate, ethanol, butyrate, and butanol.
Together, these inventive features cover methods of modulating chemical production by varying substrate mixtures of different oxidation states to control redox cofactors and metabolic outputs in anaerobic and fermentative organisms without genetic modification, enabling fine-tuned control of chemical yields and fermentation profiles.
Stated Advantages
Enables fine-tuned control of reduced electron carrier production without requiring genetic engineering.
Allows modulation of metabolic state and chemical output by varying substrate oxidation states and ratios.
Reduces time, cost, and risks associated with metabolic pathway modification.
Enhances flexibility and configurability of microbial fermentation processes using native pathways.
Improves yields of desired chemicals and reduces the production of undesirable side-products.
Documented Applications
Regulation of electron carrying cofactors availability for fine-tuning metabolite output in biological production processes.
Production of biologically produced products including small molecules, therapeutics, bulk materials, and polymers.
Bioremediation for removal or neutralization of contaminants in polluted land and water surfaces.
Agile, expedient manufacturing of specialty materials or point of need manufacturing for commercial and military technologies.
Medical and pharmaceutical applications for soldier health and well-being.
Decontamination of military environments and modulation of microbiomes to enhance soldier performance.
Interested in licensing this patent?