HTP Genomic Engineering Platform for Microbial Strain Rehabilitation

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Solution Overview

Problem

Traditional microbial strain improvement programs are inefficient, haphazard, and lead to industrial strains with a high detrimental mutagenic load, stagnating performance improvements and requiring rehabilitation.

Innovation Solution

A high-throughput (HTP) microbial genomic engineering platform that integrates molecular biology, automation, and advanced machine learning, utilizing HTP genetic design libraries derived from scientific insight and iterative pattern recognition to efficiently screen and combine genomic alterations for improved product production.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If traditional mutagenesis processes are used to improve microbial strain performance, then product productivity and yield can be increased, but the detrimental mutagenic load accumulates and stagnates further improvement

Engineering Contradiction:
Improveproduct productivityVSAvoiddetrimental mutagenic load
Core Design Contradiction:
ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent extracts and removes detrimental mutations from industrial microbial strains through targeted gene editing techniques. By identifying and eliminating harmful genetic alterations accumulated during traditional mutagenesis, the strain is rehabilitated to restore its original performance potential while removing the mutagenic burden that was stagnating further improvement.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent applies precise parameter changes to microbial genomes by introducing specific point mutations, deletions, or modifications at targeted locations using advanced gene editing tools. This allows for controlled optimization of biosynthetic pathways without the random, haphazard changes characteristic of traditional mutagenesis, thereby improving productivity without accumulating detrimental mutagenic load.

Inventive Principle:
Principle #35Parameter changes

2Productivity

If traditional mutagenesis and screening methods are used, then improved strains can be obtained, but the process is time-consuming and inefficient

Engineering Contradiction:
Improvestrain improvement efficiencyVSAvoidtime for strain improvement
Core Design Contradiction:
ProductivityVSLoss of time

Solution Approach 1:

The patent performs preliminary computational analysis and in silico screening to identify promising genetic modifications before implementing them in actual microbial strains. By pre-screening potential gene edits using bioinformatics tools and predictive models, the research team can prioritize the most promising candidates for experimental validation, dramatically reducing the time and resources required for strain improvement.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent replaces traditional mechanical and chemical mutagenesis methods with computational and information-based approaches. By using bioinformatics, machine learning algorithms, and in silico modeling to guide strain development, the process transitions from random, trial-and-error experimentation to a rational, predictive design approach that is both faster and more efficient.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

3Productivity

If random mutagenesis is used to improve microbial strains, then beneficial mutations can be discovered, but the process is haphazard and lacks direction

Engineering Contradiction:
Improvebeneficial mutation discoveryVSAvoidprocess directionality
Core Design Contradiction:
ProductivityVSEase of operation

Solution Approach 1:

The patent implements feedback loops where experimental results from microbial strain performance are fed back into computational models to refine predictions and guide subsequent genetic modifications. This iterative process uses real data from laboratory experiments to update and improve the accuracy of in silico predictions, creating a directed search strategy that learns from each iteration and becomes increasingly efficient at identifying beneficial mutations.

Inventive Principle:
Principle #23Feedback

Solution Approach 2:

The patent develops a universal, multi-functional platform that integrates computational modeling, bioinformatics analysis, and experimental validation into a unified strain improvement workflow. This integrated system can be applied across different microbial species and biosynthetic pathways, providing a generalizable approach that directs the search for beneficial mutations in a systematic rather than haphazard manner.

Inventive Principle:
Principle #6Universality (Multi-functionality)

Data Source

PatentUS20220275361A1HTP genomic engineering platform
Publication Date: 2022.09.01 GINKGO BIOWORKS INC
  • US20220275361A1 patent drawing
  • US20220275361A1 patent drawing
  • US20220275361A1 patent drawing

AI summary

The present disclosure provides a HTP microbial genomic engineering platform that is computationally driven and integrates molecular biology, automation, and advanced machine learning protocols. This integrative platform utilizes a suite of HTP molecular tool sets to create HTP genetic design libraries, which are derived from, inter alga, scientific insight and iterative pattern recognition. The HTP genomic engineering platform described herein is microbial strain host agnostic and therefore can be implemented across taxa. Furthermore, the disclosed platform can be implemented to modulate or improve any microbial host parameter of interest.