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-11091783-B2
Publication Date
2021-08-17
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 for fine-tuning of the metabolic state of anaerobic fermentative organisms via controlled regeneration of reduced electron carriers, such as NADH and NADPH, thereby modulating chemical production. The fermentative cells may include species such as Clostridium acetobutylicum and Clostridium saccharoperbutylacetonicum, and the carbohydrates fed with galacturonate can comprise substances like glucose, mannose, galactose, fructose, and others.
The problem being solved addresses the limitations of traditional fermentation technology and metabolic engineering approaches. Conventional methods focus primarily on improving product yield but struggle with substrates having different oxidation states, co-utilization of mixed substrates, and the need for genetic modifications to optimize redox cofactor availability. Existing processing technologies fail to efficiently handle complex inputs like waste materials and often cannot finely control metabolic outputs or achieve robust production without genetic engineering. The invention overcomes these issues by enabling co-utilization of substrates with different oxidation states without genetic modification, allowing modulation of intracellular redox environment and metabolic outputs through substrate ratio adjustment.
By employing co-feeding of galacturonate (a more oxidized substrate) and carbohydrates (more reduced substrates), the embodiments provide a method to regulate the production of reduced electron carriers and thereby control metabolic pathways and fermentation products such as acetate and butyrate. This metabolic control permits producing chemicals at defined ratios without the need for genetic engineering of the fermentative organisms. The method enables continuous tuning of the redox environment inside cells, resulting in fine-tuned control of metabolite outputs and reducing undesirable side product formation.
Claims Coverage
The patent contains one independent claim focused on methods of chemical production by co-feeding fermentative cells with combinations of galacturonate or its polymers and carbohydrates at varied proportions.
Method of producing chemicals with controlled substrate proportions
A method comprising providing fermentative cells, co-feeding a feedstock mixture comprising galacturonate or galacturonate polymers with carbohydrates at a first proportion to produce a first chemical, altering the feedstock mixture to a second proportion, and thereafter producing a second chemical by co-feeding the altered mixture. This method emphasizes modulating chemical production by changing ratios of substrate types fed to the fermentative cells.
The main inventive feature is the controlled modulation of metabolic output by adjusting the proportion of galacturonate-based substrates to carbohydrates fed to fermentative cells, enabling switching between or tuning production of different chemicals such as acetate and butyrate without genetic modification.
Stated Advantages
Allows fine-tuned control of the metabolic state and redox environment of fermentative organisms via co-feeding substrate mixtures with distinct oxidation states.
Modulates production of desired chemicals like acetate and butyrate by altering substrate ratios without requiring genetic engineering.
Reduces time, resources, and risks associated with metabolic engineering by utilizing native pathways for co-utilization and metabolic control.
Enables handling of complex inputs including waste materials and supports more flexible, configurable, and robust fermentation processes.
Facilitates production of biologically derived products with optimized yields and decreased formation of undesirable side-products.
Documented Applications
Production of chemicals such as acetate, butyrate, acetone, butanol, ethanol, and other biologically produced products.
Regulating electron carrier availability for balanced metabolite output and optimized chemical production in fermentative organisms.
Bioremediation applications for removal or neutralization of contaminants in polluted land and water.
Agile manufacturing of specialty materials and point-of-need manufacturing in commercial and military contexts.
Medical and pharmaceutical applications including increasing antibiotic susceptibility of anaerobic organisms and modulation of microbiomes for improved soldier performance and military environment decontamination.
Interested in licensing this patent?