Microbial Fatty Acid Production via Micro-Aerobic Cultivation
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Solution Overview
Problem
Current microbial production methods for fatty acids face challenges in achieving high yields and rates due to limitations in ATP and reducing equivalent availability, particularly under anaerobic conditions, leading to costly and inefficient oxygen-rich processes.
Innovation Solution
A new micro-aerobic/anaerobic cultivation method involving aerobic growth followed by oxygen lean conditions, combined with genetic modifications such as overexpressing NAD-dependent formate dehydrogenase and acyl-ACP thioesterase, to enhance fatty acid production even under anaerobic conditions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Speed
If oxygen-rich respiration is used for microbial production, then cell growth rate and yield are improved, but product yield of fatty acids is reduced
Solution Approach 1:
The patent implements a two-stage cultivation method where the first stage uses aerobic conditions for cell growth, and the second stage switches to anaerobic conditions for fatty acid production. This periodic transition allows the system to benefit from both aerobic growth efficiency and anaerobic product accumulation, resolving the contradiction between cell growth rate and fatty acid yield
Solution Approach 2:
The patent dynamically adjusts dissolved oxygen levels during the cultivation process, transitioning from high oxygen availability during growth phase to oxygen limitation during production phase. This dynamic control allows optimization of both cell growth and fatty acid synthesis at different time points, eliminating the need to choose between the two opposing requirements
2Productivity
If aerobic fermenters are used, then cell growth is efficient, but capital cost and operating cost increase
Solution Approach 1:
The patent uses periodic switching between aerobic and anaerobic conditions, allowing the use of simpler anaerobic fermentation equipment for the production phase while using aerobic conditions only temporarily for growth. This reduces the need for expensive oxygen supply systems and high-energy aeration equipment that would be required for continuous aerobic operation
Solution Approach 2:
The patent changes the dissolved oxygen parameter from high to low/zero during different phases of cultivation. By controlling oxygen availability as a switchable parameter rather than maintaining constant high levels, the system achieves efficient growth when needed while avoiding the continuous energy costs and equipment requirements of aerobic fermentation
3Productivity
If anaerobic fermentation is used, then product formation is high, but cell growth is poor and competing fermentation products are formed
Solution Approach 1:
The patent implements sequential aerobic-anaerobic cultivation where aerobic growth occurs first to build sufficient cell mass, followed by anaerobic production phase. This temporal separation ensures that cells reach adequate biomass before switching to product formation mode, avoiding the problem of poor cell growth that would occur if anaerobic conditions were used from the beginning
Solution Approach 2:
The patent performs preliminary aerobic growth to establish sufficient cell mass and metabolic capacity before transitioning to anaerobic conditions for fatty acid production. This preliminary action ensures that cells have adequate resources and enzymatic machinery ready for high-level product synthesis when anaerobic conditions are imposed, preventing the cell growth deficiency that would occur without this preparatory phase
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 results in a significant increase in fatty acid production, up to tenfold, while reducing operational costs and maintaining high yields, with the ability to produce fatty acids under oxygen lean or anaerobic conditions without the need for excessive oxygen supply.
Implementation Method 1
under anaerobic conditions, pyruvate dehydrogenase activity is much reduced and the reaction of converting pyruvate to acetyl-CoA is mainly carried out by the enzyme pyruvate formate lyase (PFL). However, the reaction catalyzed by pyruvate formate lyase does not produce any NADH, but produces formate instead.
Implementation Method 2
The growing fatty acid chain is carried between these active sites while attached covalently to the phosphoantetheine prosthetic group of an acyl carrier protein (ACP), and is released from the ACP by the action of a thioesterase (TE) upon reaching a carbon chain length of e.g., 16
Data Source
AI summary
This invention describes a method of using microbial to produce fats, such as fatty acids and their derivatives, or products derived from the fatty acid synthesis cycle, such as hydroxyfatty acids, methyl ketones, and the like.