Engineered Yeast Collagen Production With Ascorbate Hydroxylation
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Solution Overview
Problem
Traditional leather production is wasteful and environmentally harmful, with increasing demand for animal hides straining food sources and contributing to environmental degradation, while existing methods struggle to produce collagen in quantities and forms needed for diverse commercial applications, requiring new sources and methods for biofabricated materials with leather-like aesthetics and functionalities.
Innovation Solution
Genetically engineered yeast strains are developed to produce recombinant collagen by integrating genes for an α ketoglutarate transporter and an ascorbate synthesis pathway, enabling the yeast to hydroxylate proline and lysine residues and produce ascorbate, thereby enhancing collagen production and hydroxylation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If traditional leather production methods are used, then leather products can be manufactured, but environmental harm and waste increase while food sources are strained
Solution Approach 1:
The patent creates a copy of collagen (the primary component of leather) through recombinant DNA technology in yeast cells. Instead of using animal hides, the invention synthesizes collagen proteins that mimic the structure and function of natural leather collagen, thereby producing leather-like materials without harming animals or the environment
Solution Approach 2:
The patent replaces the biological system of animal hide processing with a biochemical production system using genetically engineered yeast. The mechanical and chemical processes traditionally used to extract and process collagen from animal hides are substituted with controlled biological synthesis in a fermentation system
2Quantity of substance
If existing recombinant collagen production methods are used, then some collagen can be produced, but insufficient quantities and forms are obtained for diverse commercial applications
Solution Approach 1:
The patent modifies multiple parameters of the collagen production system: the genetic sequence of collagen genes optimized for yeast expression, the cultivation conditions of yeast cells, and the post-translational modification conditions. These parameter changes enable the production of collagen in various forms (soluble, insoluble, fibrillar) and at scaled quantities suitable for different commercial applications
Solution Approach 2:
The patent creates a universal production platform using yeast cells that can produce different types of collagen (Type I, Type III, and other types) by transforming them with appropriate collagen genes. This single system serves multiple functions: producing various collagen types, achieving different structural forms, and meeting diverse commercial requirements
3Manufacturing precision
If yeast strains without ascorbate synthesis capability are used, then production is simpler, but hydroxylation of collagen is insufficient
Solution Approach 1:
The patent performs preliminary action by engineering the yeast cells in advance to possess ascorbate synthesis capability through genetic modification. The yeast are pre-equipped with the necessary enzymatic pathways (GDP-L-Gal phosphorylase, inositol-phosphate phosphatase, GDP-Mannose-3,5-epimerase, and L-gulono-1,4-lactone oxidase) before collagen production begins, ensuring that hydroxylation can proceed efficiently without additional complexity during the production process
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The engineered yeast strains efficiently produce collagen with improved hydroxylation, addressing the need for biofabricated materials with desired properties, such as strength, uniformity, and aesthetic appeal, offering a sustainable alternative to traditional leather production.
Implementation Method 1
The yeast strains are engineered to produce increased amounts of hydroxylated protein (e.g., collagen) and carbohydrates by improving the hydroxylation reaction through the use of an α ketoglutarate transporter (kgtP)
Implementation Method 2
The yeast cells may be further modified to express and/or overexpress a protein which hydroxylates proline and/or lysine residues to yield hydroxyproline, 3-hydroxyproline (Hyp) and hydroxylysine (Hyl)
Implementation Method 3
The yeast strains are engineered to produce increased amounts of hydroxylated protein (e.g., collagen) and carbohydrates by improving the hydroxylation reaction through the use of an α ketoglutarate transporter (kgtP) and/or one or more polypeptides that enable an ascorbate synthesis pathway to function
Data Source
AI summary
This invention relates to genetically engineered strains of yeast and methods for producing recombinant protein (e.g., collagen). Recombinant protein of the present invention is used to produce biofabricated leather or a material having leather-like properties containing recombinant or engineered collagen. The yeast strains are engineered to produce ascorbate and/or increased production of α ketoglutarate.