Engineered Microbes for Lipid Overproduction from Cellulosic Biomass

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Solution Overview

Problem

Current methods for microbial biofuel production from cellulosic biomass are limited by high costs and energy requirements due to the need for glucose-based feedstocks and the negative feedback loops triggered by saturated fatty acid production, which inhibit lipid synthesis.

Innovation Solution

Engineering microbes to utilize non-traditional carbon sources like xylose by amplifying upstream and downstream metabolic pathways, specifically through genetic modifications that increase expression of genes such as xylose reductase, xylitol dehydrogenase, xylose isomerase, xylulokinase, diacylglycerol acyltransferase, acetyl-CoA carboxylase, stearoyl-CoA desaturase, and ATP-citrate lyase, to enhance lipid synthesis without feedback inhibition.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If glucose-based feedstocks are used for microbial oil production, then lipid synthesis can be achieved, but production costs and energy requirements increase significantly

Engineering Contradiction:
Improvelipid synthesis rateVSAvoidenergy requirements
Core Design Contradiction:
ProductivityVSUse of energy by moving object

Solution Approach 1:

The patent changes the carbon source parameter from glucose to cellulosic biomass (xylose, arabinic acid, D-arabitol), fundamentally altering the feedstock type to reduce production costs and energy requirements while maintaining lipid synthesis capability through engineered metabolic pathways

Inventive Principle:
Principle #35Parameter changes

2Productivity

If carbon flux is increased into fatty acid synthesis pathways, then lipid production increases, but saturated fatty acid levels rise and activate negative feedback loops that inhibit lipid synthesis

Engineering Contradiction:
Improvelipid production rateVSAvoidfeedback inhibition
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The patent extracts and eliminates the harmful negative feedback loop by removing or modifying the regulatory mechanisms that cause saturated fatty acids to inhibit lipid synthesis, allowing continuous carbon flux into lipid pathways without feedback inhibition

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent introduces alternative feedback mechanisms or removes the harmful feedback loop entirely, replacing the natural negative feedback from saturated fatty acids with engineered metabolic control that maintains high carbon flux through lipid synthesis pathways without inhibition

Inventive Principle:
Principle #23Feedback

3Productivity

If traditional carbon sources like glucose are used, then microbial growth is supported, but the high cost of feedstock reduces cost-effectiveness

Engineering Contradiction:
Improvemicrobial growth rateVSAvoidproduction cost
Core Design Contradiction:
ProductivityVSEase of manufacture

Solution Approach 1:

The patent changes the carbon source parameter from expensive glucose to low-cost cellulosic biomass components (xylose, arabinic acid, D-arabitol), fundamentally altering the feedstock to reduce production costs while maintaining microbial growth and lipid production capabilities

Inventive Principle:
Principle #35Parameter changes

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

This approach achieves significant increases in fatty acid and triacylglycerol production rates and yields, allowing for efficient conversion of carbon sources into lipids, thereby reducing production costs and energy requirements.

Implementation Method 1

a xylose reductase (XYL1) gene product and a xylitol dehydrogenase (XYL2) gene product

Methodology Applied
Scientific EffectReduction: Reduction

Implementation Method 2

a xylose reductase (XYL1) gene product and a xylitol dehydrogenase (XYL2) gene product

Methodology Applied
Scientific EffectOxidation: Oxidation

Implementation Method 3

an acetyl-coA carboxylase (ACC) gene product

Methodology Applied
Scientific EffectCarboxylation: Chemical Bonding

Implementation Method 4

a diacylglycerol acyltransferase (DGA) gene product

Methodology Applied
Scientific EffectEsterification: Chemical Bonding

Implementation Method 5

an ATP-citrate lyase (ACL) gene product

Methodology Applied
Scientific EffectLysis: Chemical Bonding

Implementation Method 6

a stearoyl-CoA-desaturase (SCD) gene product

Methodology Applied
Scientific EffectDesaturation: Chemical Bonding

Data Source

PatentUS9096876B2Engineered microbes and methods for microbial oil overproduction from cellulosic materials
Publication Date: 2015.08.04 MASSACHUSETTS INST OF TECH
  • US9096876B2 patent drawing
  • US9096876B2 patent drawing
  • US9096876B2 patent drawing

AI summary

The invention relates to engineering microbial cells for utilization of cellulosic materials as a carbon source, including xylose.