Microbial Organisms for Primary Alcohol Production

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Solution Overview

Problem

Current methods for producing primary alcohols are inefficient and costly, as they often result in low yields of secondary or tertiary alcohols and ketones, and rely on expensive feedstocks like ethylene, with existing biosynthetic pathways being energy-intensive and multi-step.

Innovation Solution

Development of non-naturally occurring microbial organisms with a malonyl-CoA-independent fatty acid synthesis pathway and an acyl-reduction pathway, expressing specific enzymes to produce primary alcohols under anaerobic conditions, allowing for higher yields and the use of renewable feedstocks.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Device complexity

If oxidation of n-paraffins is used to produce primary alcohols, then production process is simplified, but yield of primary alcohols is low and mixture of secondary alcohols, tertiary alcohols or ketones is produced

Engineering Contradiction:
Improveprocess complexityVSAvoidproduct selectivity
Core Design Contradiction:
Device complexityVSManufacturing precision

Solution Approach 1:

The invention changes the biochemical parameters of the organism by introducing heterologous genes (fadE, fabG, fabH) to create a malonyl-CoA-independent fatty acid synthesis pathway. This parameter change in the metabolic route enables high-selectivity production of primary alcohols from n-paraffin oxidation, resolving the contradiction between process simplification and product selectivity.

Inventive Principle:
Principle #35Parameter changes

2Productivity

If current biosynthetic pathways are used for LCA production, then fatty acid synthesis occurs, but energy consumption is high and product yield is low

Engineering Contradiction:
Improveproduct yieldVSAvoidenergy consumption
Core Design Contradiction:
ProductivityVSUse of energy by moving object

Solution Approach 1:

The invention extracts and eliminates the malonyl-CoA-dependent steps from the fatty acid synthesis pathway by introducing a malonyl-CoA-independent pathway. This removal of energy-intensive steps (malonyl-CoA formation requiring ATP) directly reduces energy consumption and increases productivity of long-chain alcohol production.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The invention changes the biochemical parameters by introducing heterologous genes (fadE, fabG, fabH) to create a malonyl-CoA-independent fatty acid synthesis pathway. This parameter change eliminates ATP-consuming steps in the pathway, directly reducing energy consumption and increasing product yield.

Inventive Principle:
Principle #35Parameter changes

3Ease of manufacture

If ethylene is used as feedstock for primary alcohol production, then production process is established, but feedstock cost is high

Engineering Contradiction:
Improveprocess establishmentVSAvoidfeedstock cost
Core Design Contradiction:
Ease of manufactureVSQuantity of substance

Solution Approach 1:

The invention changes the substrate parameter by enabling the organism to utilize n-paraffins directly through the introduced malonyl-CoA-independent pathway. This parameter change in substrate utilization allows replacement of expensive ethylene feedstock with cheaper n-paraffins, reducing feedstock cost while maintaining process establishment.

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 enables the production of primary alcohols with higher product and ATP yields, reducing production costs and energy consumption, while utilizing low-cost renewable feedstocks, thereby improving the efficiency and sustainability of the process.

Implementation Method 1

ketoacyl-CoA acyltransferase or ketoacyl-CoA thiolase

Methodology Applied
Scientific EffectCondensation reaction: Chemical Bonding

Implementation Method 2

3-hydroxyacyl-CoA dehydrogenase

Methodology Applied
Scientific EffectOxidation-reduction reaction: Redox Reactions

Implementation Method 3

enoyl-CoA hydratase

Methodology Applied
Scientific EffectHydration reaction: Chemical Bonding

Implementation Method 4

acyl-CoA reductase

Methodology Applied
Scientific EffectReduction reaction: Redox Reactions

Implementation Method 5

alcohol dehydrogenase

Methodology Applied
Scientific EffectDehydrogenation reaction: Redox Reactions

Data Source

PatentUS11613767B2Primary alcohol producing organisms
Publication Date: 2023.03.28 GENOMATICA INC
  • US11613767B2 patent drawing
  • US11613767B2 patent drawing
  • US11613767B2 patent drawing

AI summary

The invention provides a non-naturally occurring microbial organism having a microbial organism having at least one exogenous gene insertion and/or one or more gene disruptions that confer production of primary alcohols. A method for producing long chain alcohols includes culturing these non-naturally occurring microbial organisms.