Sensor-Antidote Microbial Selection for Metabolite Optimization

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Selecting optimized bacterial strains for metabolite production from large populations is challenging due to the need for efficient methods to identify strains that maximize chemical production, as existing techniques lack precision and efficiency.

Innovation Solution

Genetically modifying microorganisms to include a sensor and antidote system, where the sensor regulates antidote production based on metabolite levels, allowing for selection of strains that survive in toxin environments, thereby optimizing metabolite production through repeated genetic modifications and selection.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If traditional methods are used to select optimized bacterial strains from large populations, then the selection process becomes time-consuming and inefficient, but the complexity of the selection system increases

Engineering Contradiction:
Improvestrain selection efficiencyVSAvoidselection system complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The bacterial strain itself performs the selection function by autonomously producing the antidote in response to toxin exposure. The sensor-antidote system is integrated within the bacterium's genome, allowing it to self-regulate and self-select based on metabolite production capacity without requiring external selection apparatus or complex intervention protocols.

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

A feedback loop is established where the sensor detects metabolite concentration and regulates antidote production accordingly. The antidote then counteracts the toxin, creating a feedback mechanism where metabolite-producing strains survive and are selected, while non-producing strains die. This automatic feedback system streamlines the selection process.

Inventive Principle:
Principle #23Feedback

2Measurement precision

If the toxin concentration is increased to improve selection pressure, then the precision of metabolite production detection improves, but the number of strains that die increases

Engineering Contradiction:
Improvemetabolite detection precisionVSAvoidsurviving strain quantity
Core Design Contradiction:
Measurement precisionVSQuantity of substance

Solution Approach 1:

The system allows for dynamic adjustment of toxin concentration as a selectable parameter. By changing the toxin concentration parameter, users can optimize the balance between detection precision and surviving strain quantity according to specific experimental needs, enabling flexible control over selection stringency.

Inventive Principle:
Principle #35Parameter changes

3Productivity

If repeated rounds of genetic modification and selection are performed to optimize metabolite production, then the metabolite yield increases, but the time required for optimization increases

Engineering Contradiction:
Improvemetabolite yieldVSAvoidoptimization time
Core Design Contradiction:
ProductivityVSLoss of time

Solution Approach 1:

The selection process enables continuous optimization cycles where surviving strains from one round immediately become the basis for the next round of genetic modification and selection. The sensor-antidote-toxin system remains active throughout multiple generations, allowing uninterrupted sequential optimization without requiring system reconfiguration between rounds.

Inventive Principle:
Principle #20Continuity of useful action

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 method enables the rapid identification and optimization of bacterial strains for metabolite production, significantly increasing the yield and robustness of metabolite production by selecting strains that produce sufficient antidote to survive in increasing toxin concentrations.

Implementation Method 1

the sensor or metabolite binding molecule is an allosteric biomolecule that undergoes a conformation change upon binding a desired chemical or metabolite resulting in a change in gene regulation

Methodology Applied
Scientific EffectAllosteric conformation change:

Data Source

PatentUS11603528B2Methods for selecting microbes from a diverse genetically modified library to detect and optimize the production of metabolites
Publication Date: 2023.03.14 PRESIDENT & FELLOWS OF HARVARD COLLEGE
  • US11603528B2 patent drawing
  • US11603528B2 patent drawing
  • US11603528B2 patent drawing

AI summary

The present invention relates to genetically modified bacteria and methods of optimizing genetically modified bacteria for the production of a metabolite.