Argyrin Biosynthesis Enzyme Segmentation

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Solution Overview

Problem

Current methods for producing Argyrins rely on natural producer organisms, limiting control over production rates and product specificity, with no established nucleic acid sequences or amino acid sequences for synthetic pathway enzymes available for manipulation.

Innovation Solution

Providing amino acid sequences for synthetic pathway enzymes and corresponding nucleic acid sequences that encode these enzymes, enabling genetic manipulation of microorganisms to produce Argyrins, including the use of genetically modified microorganisms and cell-free enzyme systems for Argyrin synthesis.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If natural producer organisms are used for Argyrin production, then production is possible, but control over production rates and product specificity is limited

Engineering Contradiction:
ImproveArgyrin production rateVSAvoidcontrol over production and product specificity
Core Design Contradiction:
ProductivityVSAdaptability or versatility

Solution Approach 1:

The patent segments the Argyrin biosynthetic pathway into individual enzymatic steps, each catalyzed by a specific enzyme (e.g., Arg1, Arg2, Arg3, Arg4, Arg5). This segmentation allows independent manipulation of each enzyme through genetic modification, enabling precise control over production rates and product specificity without being constrained by the natural producer organism's overall metabolic regulation.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent enables dynamic control of the biosynthetic pathway by providing genetically modified organisms where enzyme expression levels can be adjusted. The synthetic pathway enzymes can be upregulated or downregulated independently, allowing the system to adapt production rates and product distribution according to desired outcomes, transforming a static natural system into a dynamically controllable one.

Inventive Principle:
Principle #15Dynamics

2Adaptability or versatility

If genetic manipulation is implemented to improve production control, then adaptability increases, but device complexity increases due to lack of established sequences

Engineering Contradiction:
Improveproduction control capabilityVSAvoidgenetic manipulation complexity
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent performs preliminary action by identifying, sequencing, and characterizing all the enzymes involved in the Argyrin biosynthetic pathway before genetic manipulation is attempted. The complete amino acid sequences and corresponding nucleic acid sequences of enzymes Arg1 through Arg5 are provided in advance, creating a ready-to-use genetic toolkit that simplifies subsequent genetic engineering efforts and reduces the complexity of implementation.

Inventive Principle:
Principle #10Preliminary action

3Quantity of substance

If standard isolation and purification methods are used, then Argyrins can be obtained, but manufacturing precision and product specificity are limited

Engineering Contradiction:
ImproveArgyrin yieldVSAvoidproduct specificity
Core Design Contradiction:
Quantity of substanceVSManufacturing precision

Solution Approach 1:

The patent extracts the biosynthetic capability from the natural producer organism by isolating and cloning the individual enzyme genes (arg1, arg2, arg3, arg4, arg5). These extracted genetic elements can then be transferred to heterologous host organisms, separating the production capability from the original organism's complex metabolic network. This extraction enables precise control over which Argyrin derivatives are produced, achieving high product specificity that cannot be obtained through standard isolation and purification methods alone.

Inventive Principle:
Principle #2Taking out (Extraction)

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

Enables precise manipulation of Argyrin production in microorganisms, allowing for the production of specific Argyrin derivatives and increasing production efficiency by targeting mutations in the synthetic pathway enzymes.

Implementation Method 1

The invention provides the proteins forming part of or constituting the non-ribosomal peptide synthetases (NRPS) having the activity to catalyse at least one conversion step in the synthesis of Argyrins

Methodology Applied
Scientific EffectEnzyme catalysis: Enzyme

Data Source

PatentUS9217169B2Synthetic pathway enzymes for the production of argyrins
Publication Date: 2015.12.22 HELMHOLTZ ZENTRUM FUER INFEKTIONSFORSCHUNG GMBH
  • US9217169B2 patent drawing
  • US9217169B2 patent drawing
  • US9217169B2 patent drawing

AI summary

The invention provides the amino acid sequences comprised in or constituting the synthetic pathway enzymes participating in the production of Argyrins, as well as the nucleic acid sequences encoding the synthetic pathway enzymes participating in the production of Argyrins, as well as genetically manipulated microorganisms containing nucleic acid sequences encoding the synthetic pathway enzymes for the production of Argyrins, e.g. for inserting one or more of these coding sequences, mutating in a targeted manner one or more of these nucleic acid sequences, in a wild type producer micro-organism or in a heterologous micro-organism, for the production of Argyrins.