Synthetic Polypeptides for Pimelic Acid Biosynthesis

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Solution Overview

Problem

Current methods for producing 7-Aminoheptanoic acid (7-AHA), a key intermediate for Nylon 7 synthesis, lack economically favorable petrochemical routes, and existing biochemical pathways require improvements in enzymatic activity and substrate specificity for efficient production.

Innovation Solution

Design and construction of synthetic polypeptides with acyl-ACP thioesterase activity, specifically with amino acid substitutions at defined positions, to enhance enzymatic activity and substrate specificity for converting pimeloyl-ACP to pimelic acid, facilitating the production of 7-AHA through biosynthetic routes.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If wild-type acyl-ACP TE is used in the biochemical pathway, then the pathway can function to produce pimelic acid, but the enzymatic activity and substrate specificity are insufficient for efficient production

Engineering Contradiction:

Improveproduction efficiency of pimelic acidVSAvoidsubstrate specificity of acyl-ACP TE

Core Design Contradiction:

ProductivityVSReliability

Solution Approach 1:

The patent applies parameter changes by modifying amino acid residues at specific positions (5, 32, 33, 35, 36, 38, 40, 45, 59, 64, 90, 111, 128, 175, and 241) in the acyl-ACP TE polypeptide sequence. These sequence modifications alter the enzymatic parameters including substrate specificity and catalytic activity, enabling the enzyme to efficiently process pimeloyl-ACP while maintaining structural stability and function.

Inventive Principle:

Principle #35Parameter changes

2Ease of manufacture

If petrochemical routes are used for producing 7-AHA, then production can proceed with established industrial methods, but there are no economically favorable routes available

Engineering Contradiction:

Improvemanufacturing feasibility of 7-AHAVSAvoideconomic viability of production

Core Design Contradiction:

Ease of manufactureVSProductivity

Solution Approach 1:

The patent replaces petrochemical manufacturing methods with a biochemical pathway utilizing engineered acyl-ACP TE enzymes. This substitution transitions from traditional petrochemical feedstock conversion to a biologically-based synthesis route using engineered microorganisms that convert renewable substrates into 7-AHA through the modified thioesterase pathway, achieving both environmental sustainability and economic viability.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

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

The synthetic polypeptides demonstrate increased enzymatic activity and improved substrate specificity, enabling more efficient production of 7-AHA, potentially replacing traditional petrochemical methods with a bio-based approach.

Implementation Method 1

synthetic polypeptides, having an acyl-ACP TE activity, useful for the production of 7-AHA, via biosynthetic routes

Methodology Applied

Scientific EffectThioesterase activity: Enzyme

Data Source

PatentUS10975363B2Materials and methods for biosynthetic manufacture and utilization of synthetic polypeptides, and products therefrom

Publication Date: 2021.04.13 INV NYLON CHEMICALS AMERICAS LLC

AI summary

Provided herein are novel, synthetic polypeptides having, for example, acyl-acyl carrier protein (ACP) thioesterase (TE) activity, including polypeptides that convert pimeloyl-ACP to pimelic acid. In some aspects, the synthetic polypeptides have advantageous enzymatic activity and/or improved substrate specificity relative to a wild type acyl-ACP TE.