Microbial Cultivation Oxygen Limitation Process

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Solution Overview

Problem

Current microbial cultivation methods for producing proteins and other valuable compounds face inefficiencies due to nutrient limitations, particularly in nitrogen and carbon, leading to low biomass yield and poor productivity.

Innovation Solution

Cultivating microorganisms in a medium with all nutrients supplied in excess and maintaining oxygen limitation by carefully controlling oxygen transfer rates to match oxygen uptake rates, ensuring that oxygen is consumed immediately without excess, thereby maintaining a constant dissolved oxygen level close to zero.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If nutrients are supplied in limited amounts to control growth, then productivity is improved, but biomass yield deteriorates

Engineering Contradiction:
ImproveproductivityVSAvoidbiomass yield
Core Design Contradiction:
ProductivityVSQuantity of substance

Solution Approach 1:

The patent extracts oxygen limitation as a separate control parameter from nutrient limitation. By specifically limiting oxygen while supplying nutrients in excess, the process decouples growth control from productivity control, allowing high biomass yield alongside high productivity in the production phase.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent changes the limiting parameter from nutrients (nitrogen, carbon) to oxygen. This parameter change transforms the physiological state of the microorganism, shifting metabolism toward product formation while maintaining high biomass levels, thereby resolving the contradiction between productivity and biomass yield.

Inventive Principle:
Principle #35Parameter changes

2Quantity of substance

If nutrients are supplied in excess, then biomass yield is improved, but productivity deteriorates

Engineering Contradiction:
Improvebiomass yieldVSAvoidproductivity
Core Design Contradiction:
Quantity of substanceVSProductivity

Solution Approach 1:

The patent separates the control of biomass accumulation from product formation by extracting oxygen as the independent limiting factor. This allows nutrients to be supplied in excess for high biomass yield while oxygen limitation drives productivity, eliminating the traditional trade-off.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent dynamically adjusts oxygen supply during the production phase to maintain oxygen limitation conditions. This dynamic control enables the system to simultaneously achieve high biomass yield from excess nutrients and high productivity through controlled oxygen uptake, adapting the metabolic state in real-time.

Inventive Principle:
Principle #15Dynamics

3Productivity

If oxygen is supplied in excess, then productivity is improved, but energy efficiency deteriorates

Engineering Contradiction:
ImproveproductivityVSAvoidenergy efficiency
Core Design Contradiction:
ProductivityVSLoss of energy

Solution Approach 1:

The patent converts the potential harm of excess oxygen (energy waste through respiration) into a beneficial control mechanism. By deliberately limiting oxygen to match uptake rates, the process prevents energy loss while maintaining high productivity, transforming what could be waste into a precise control parameter.

Inventive Principle:
Principle #22Blessing in disguise (Convert harm into benefit)

Solution Approach 2:

The patent implements feedback control by monitoring oxygen uptake rates and adjusting oxygen supply accordingly. This ensures oxygen is supplied at the exact rate needed for productivity without excess, eliminating energy inefficiency while maintaining optimal product formation rates throughout the cultivation process.

Inventive Principle:
Principle #23Feedback

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 enhances the yield of valuable compounds like phytase and biomass, improving productivity and reducing by-products, facilitating more efficient and cost-effective industrial-scale microbial production processes.

Implementation Method 1

the OTR (oxygen transfer rate) is the rate with which the oxygen is transferred from the gas phase to the liquid phase (culture broth)

Methodology Applied
Scientific EffectOxygen transfer: Absorption (physical)

Implementation Method 2

the OUR (oxygen uptake rate) is the rate with which the microorganism consumes oxygen fed to the culture broth

Methodology Applied
Scientific EffectOxygen uptake: Absorption (physical)

Data Source

PatentUS9410175B2Process for microbial production of a valuable compound
Publication Date: 2016.08.09 DSM IP ASSETS BV
  • US9410175B2 patent drawing
  • US9410175B2 patent drawing
  • US9410175B2 patent drawing

AI summary

The present invention relates to a process for the production of a valuable compound by cultivation of a microorganism comprising cultivating the microorganism in a medium wherein all nutrients are provided in excess over the whole cultivation period and wherein a suitable amount of oxygen is fed to the culture to maintain the culture under conditions of oxygen limitation.