Methanol-Based Microbial Pathways for Specific-Length Fatty Alcohol Production
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Solution Overview
Problem
Current methods for producing fatty alcohols and isopropanol are inefficient and costly due to reliance on expensive feedstocks like ethylene and multiple catalyst types, and there is a need for alternative biosynthetic pathways to enhance production yields.
Innovation Solution
Development of non-naturally occurring microbial organisms with engineered pathways, including formaldehyde fixation, formate assimilation, and methanol metabolism, combined with malonyl-CoA independent or dependent fatty acyl-CoA elongation cycles, to enhance substrate availability and selectivity for specific fatty alcohol, fatty aldehyde, or fatty acid production.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If traditional chemical synthesis methods are used for fatty alcohol production, then production capacity is maintained, but production cost increases and manufacturing precision decreases
Solution Approach 1:
The patent replaces traditional chemical synthesis methods with biological synthesis using engineered microorganisms. The mechanical/chemical system of chemical catalysts and reactors is substituted with a biological system where microorganisms perform the synthesis through metabolic pathways, thereby reducing production costs while maintaining viable production capacity
Solution Approach 2:
The patent changes the fundamental parameter of the synthesis system from chemical to biological. By using engineered microorganisms with modified metabolic pathways, the system achieves cost-effective production through biological processes rather than expensive chemical synthesis, while the production capacity is sustained through scalable fermentation processes
2Adaptability or versatility
If multiple catalyst types are used in current production methods, then various fatty alcohol products are produced, but device complexity increases
Solution Approach 1:
The patent applies universality by using a single type of microorganism that can produce multiple different fatty alcohol products. The engineered microorganism possesses versatile metabolic pathways that enable it to synthesize various fatty alcohols (such as C6, C8, C10, C12, C14, C16, C18) using the same biological system, thereby eliminating the need for multiple different chemical catalysts
Solution Approach 2:
The patent uses genetic copying and replication of engineered microorganisms to maintain consistent production capabilities. The engineered strain with its modified metabolic pathways can be replicated and scaled, providing a standardized biological catalyst system that replaces the need for multiple complex chemical catalyst systems
3Productivity
If expensive feedstocks like ethylene are used, then fatty alcohol production is achieved, but loss of substance increases
Solution Approach 1:
The patent fundamentally changes the feedstock parameter from expensive petrochemical feedstocks like ethylene to inexpensive renewable feedstocks such as glucose, glycerol, or other sugars. This parameter change enables cost-effective production while reducing substance loss, as the biological conversion of these inexpensive feedstocks to fatty alcohols occurs with high efficiency through engineered metabolic pathways
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 microbial organisms significantly increase the yield and efficiency of fatty alcohol, fatty aldehyde, and isopropanol production, providing a cost-effective alternative to traditional chemical synthesis.
Implementation Method 1
a) a methanol dehydrogenase to a formaldehyde and generate reducing equivalents
Implementation Method 2
b) a hexulose-6-phosphate synthase to condense the formaldehyde with a ribulose-5-phosphate to form a hexulose-6-phosphate
Implementation Method 3
c) a 6-phospho-3-hexuloisomerase to isomerize the hexulose-6-phosphate to a fructose-6-phosphate
Implementation Method 4
d) a phosphotransacetylase to convert the acetyl-CoA to an acetyl-phosphate
Implementation Method 5
e) an acetate kinase to convert the acetyl-phosphate to an acetate and generate an ATP
Implementation Method 6
The MI-FAE cycle can include a thiolase, a 3-oxoacyl-CoA reductase, a 3-hydroxyacyl-CoA dehydratase and an enoyl-CoA reductase
Implementation Method 7
a 3-oxoacyl-CoA reductase
Implementation Method 8
a 3-hydroxyacyl-CoA dehydratase
Implementation Method 9
an enoyl-CoA reductase
Implementation Method 10
The termination pathway can include a fatty acyl-CoA reductase
Data Source
AI summary
The invention provides non-naturally occurring microbial organisms having a formaldehyde fixation pathway, a formate assimilation pathway, and/or a methanol metabolic pathway in combination with a fatty alcohol, fatty aldehyde, fatty acid or isopropanol pathway, wherein the microbial organisms selectively produce a fatty alcohol, fatty aldehyde or fatty acid of a specified length or isopropanol. The microbial organisms provided advantageously enhance the production of substrates and/or pathway intermediates for the production of chain length specific fatty alcohols, fatty aldehydes, fatty acids or isopropanol. In some aspects, the microbial organisms of the invention have select gene disruptions or enzyme attenuations that increase production of fatty alcohols, fatty aldehydes or fatty acids. The invention additionally provides methods of using the above microbial organisms to produce a fatty alcohol, a fatty aldehyde, a fatty acid or isopropanol.