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Polylactic Acid (PLA) Precursor (Lactic Acid) Engineering Service

Polylactic Acid (PLA) is a leading bio-based, biodegradable material used across packaging, biomedical, and textile industries. Its widespread adoption is hindered by the current dependence on fermentation, which suffers from low efficiency of lactic acid fermentation and insufficient purity of precursors , leading to a high cost compared to petroleum-derived plastics.

CD Biosynsis offers a synthetic biology service focused on optimizing the microbial production of the PLA precursor, Lactic Acid. Our core strategy involves the modification of the lactic acid metabolism pathway in the host organism to maximize carbon flux towards lactate and minimize byproducts. This is combined with the directed evolution of lactic acid dehydrogenase (LDH) in Escherichia coli to enhance its specific activity, stability, and stereospecificity. This approach aims to establish a cost-effective, high-yield, and high-purity bioproduction route for the PLA building block.

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Pain Points Solutions Advantages Process FAQ

Pain Points

Achieving cost parity for bio-based PLA requires overcoming these fermentation and enzyme bottlenecks:

  • Low Fermentation Efficiency: Microbial fermentation often results in a low yield (g/L/h) due to metabolic bottlenecks and end-product inhibition by Lactic Acid.
  • Insufficient Precursor Purity: Production of side products (e.g., ethanol, acetate) leads to insufficient purity of precursors , complicating downstream purification for polymerization and affecting final PLA quality.
  • High Production Cost: The combination of low efficiency and complex purification contributes to the high cost of bio-based Lactic Acid, hindering its competitiveness.
  • Stereospecificity Requirement: PLA material properties depend heavily on the stereoisomeric purity (D- or L-lactic acid), which requires highly specific enzyme activity.

A cost-competitive solution must focus on maximizing the flux and purity of the desired Lactic Acid stereoisomer.

Solutions

CD Biosynsis applies advanced metabolic engineering and enzyme evolution to optimize Lactic Acid production:

Modification of the Lactic Acid Metabolism Pathway

           

We employ genome editing to knock out competing pathways (e.g., ethanol or acetate pathways) and optimize transport systems to enhance carbon flux toward Lactic Acid.

Directed Evolution of Lactic Acid Dehydrogenase (LDH)

We use molecular evolution techniques to create LDH variants with enhanced specific activity, tolerance to low pH , and improved stereospecificity (L- or D-lactate production).

Cofactor Regeneration Optimization

We tune the host's central metabolism to balance NADH/NAD+ regeneration , a crucial factor for sustained, efficient activity of Lactic Acid Dehydrogenase.

Host Tolerance Engineering

We modify cell membranes or regulatory genes to increase the host's resistance to acidic conditions and high lactate concentrations, allowing for high-titer fermentation.

This systematic approach is focused on optimizing microbial efficiency to produce high-purity Lactic Acid at potentially lower costs.

Advantages

Our Lactic Acid engineering service is dedicated to pursuing the following production goals:

Maximized Carbon Flux

Metabolic pathway modification aims to significantly increase the final molar yield of Lactic Acid from the carbon source.

High Precursor Purity

Knockout of competing pathways aims to minimize byproducts , simplifying downstream purification steps for polymerization.

Cost Reduction Potential

Higher titer and purity are focused on reducing overall production costs , making bio-PLA more competitive. [Image of Cost Reduction Icon]

Controlled Stereospecificity

Engineered LDH aims to achieve high purity of the desired L- or D-Lactic Acid isomer, which is critical for final PLA material properties .

Robust Host Performance

Tolerance engineering is focused on ensuring the host can perform efficiently under harsh, high-concentration fermentation conditions .

We provide a biosynthetic platform aimed at overcoming the efficiency and cost challenges of Lactic Acid bioproduction for PLA.

Process

Our Lactic Acid strain engineering service follows a standardized, iterative research workflow:

  • Metabolic Analysis and Target Identification: Map the host's native metabolism and identify all competing pathways and bottlenecks that divert carbon away from Lactic Acid.
  • Pathway Knockout and Optimization: Utilize genome editing to delete genes for byproduct formation and overexpress key glycolytic enzymes to enhance flux.
  • LDH Directed Evolution: Generate mutant libraries of Lactic Acid Dehydrogenase and screen for variants with increased activity, low pH tolerance, and high stereoselectivity .
  • NADH/NAD+ Balance Tuning: Integrate engineered circuits to ensure a sufficient supply of the NADH cofactor essential for the continuous activity of LDH.
  • Fermentation Performance Validation: Test the final engineered strain in fed-batch fermentation to assess volumetric productivity, final titer, and stereoisomeric purity .
  • Result Report Output: Compile a detailed Experimental Report including genome modification maps, LDH enzyme data, and fermentation metrics (yield, purity, cost parameters) , supporting industrial adoption.

Technical communication is maintained throughout the process, focusing on timely feedback regarding metabolic flux and enzyme performance.

Explore the potential for sustainable, high-purity Lactic Acid production. CD Biosynsis provides customized strain and enzyme engineering solutions:

  • Detailed Metabolic Flux and Purity Analysis Report , illustrating the success of pathway modifications and byproduct minimization.
  • Consultation on fermentation strategies optimized for high-titer, low-pH Lactic Acid production.
  • Experimental reports include complete raw data on enzyme kinetics, stereospecificity, and final titer/yield , essential for polymerization and commercial assessment.
   

FAQ (Frequently Asked Questions)

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Why is high purity Lactic Acid critical for PLA?

High Lactic Acid purity is essential because impurities, especially byproducts or residual sugars, can interfere with the polymerization process (ring-opening polymerization of lactide) and negatively affect the molecular weight and final properties of the PLA polymer.

How does stereospecificity affect PLA?

PLA can be made from L- or D-Lactic Acid. Pure L-PLA (PLLA) is crystalline and strong, while pure D-PLA (PDLA) is similar. Mixing them creates stereocomplex PLA , which has a significantly higher melting temperature and increased thermal stability , expanding its industrial uses.

What is the role of the competing pathway knockout?

In many hosts (like E. coli), carbon is naturally converted into multiple products (e.g., acetate, ethanol) to satisfy the cell's energy and growth needs. Knocking out these competing pathways forces the carbon to flow predominantly down the desired Lactic Acid route, increasing yield and purity.

Why is E. coli chosen over natural Lactic Acid bacteria?

E. coli is often chosen because it is genetically well-characterized, has a fast growth rate (high productivity) , and can be engineered to utilize a wider range of low-cost feedstocks (e.g., lignocellulosic sugars) than some traditional Lactic Acid bacteria.

What is the estimated project timeline?

A project involving combined metabolic pathway modification and enzyme directed evolution typically requires 20-24 weeks for final strain delivery and comprehensive performance validation.

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