Analysis of Poly-3-Hydroxybutyrate Production with Different Microorganisms Using the Dynamic Simulations for...

Area of Science:

• Biotechnology and metabolic engineering
• Sustainable bioprocessing
• Synthetic biology

Background:

• Growing environmental concerns drive interest in biodegradable bioplastics like poly-3-hydroxybutyrate (PHB) as alternatives to conventional plastics.
• High production costs and the yield-biomass trade-off hinder the industrial viability of PHB.
• Optimization of bioprocesses is crucial for enhancing product yields and economic feasibility.

Purpose of the Study:

• To present Dynamic Simulations for Evaluation of Economic Potential (DySEEP), a novel approach integrating dynamic flux balance analysis (DFBA) with economic metrics.
• To analyze and optimize the production of PHB in recombinant microbial strains, considering the trade-off between biomass and product formation.
• To identify specific metabolic engineering targets and bioreactor operation strategies for enhanced PHB production.

Main Methods:

• Implementation of Dynamic Flux Balance Analysis (DFBA) to simulate cellular metabolism over time.
• Integration of an economic metric within the DFBA framework to evaluate the economic potential of bioprocesses.
• Case study analysis of poly-3-hydroxybutyrate (PHB) production in engineered microbial hosts, including growth-associated and non-growth-associated production modes.

Main Results:

• DySEEP successfully highlighted the trade-off between biomass and PHB formation, crucial for intracellular metabolites.
• For growth-associated PHB production, positive cash flow was achieved at a yield of 0.37 g/g, with maximum theoretical profit at 0.50 g/g.
• Identified potential genetic targets for metabolic engineering, including knockouts/downregulation of specific pathways (e.g., pentose phosphate pathway, acetate production, TCA cycle).
• For non-growth-associated production, optimal glucose utilization strategies were determined for achieving positive cash flow (60% production phase) and maximum profit (80% production phase).

Conclusions:

• DySEEP provides a valuable framework for optimizing bioprocess economics by balancing metabolic objectives.
• The study provides actionable insights for both metabolic engineering strategies and bioreactor operation to enhance PHB yield and profitability.
• The findings contribute to the development of sustainable and economically viable bioplastic production methods.