Computationally Prospecting Potential Pathways from Lignin Monomers and Dimers toward Aromatic Compounds

Area of Science:

• Biotechnology and Synthetic Biology
• Metabolic Engineering
• Biocatalysis

Background:

• Lignin depolymerization yields heterogeneous aromatic products, posing challenges for valorization.
• Microbial pathways can funnel these intermediates to central products for chemical synthesis.
• Existing pathways are known for limited organisms, necessitating new designs.

Purpose of the Study:

• To computationally design novel pathways for funneling lignin-derived aromatics using the novoStoic tool.
• To explore enzymatic cleavage pathways for lignin dimers.
• To leverage enzyme promiscuity for efficient lignin valorization.

Main Methods:

• Application of the de novo pathway design tool, novoStoic.
• Utilizing reaction rules and known enzymatic conversions to hypothesize new pathways.
• Identifying mass-balanced biochemical networks for metabolite conversion.

Main Results:

• Designed alternative pathways for funneling S, G, and H lignin monomers.
• Explored cleavage pathways for β-1 and β-β lignin dimers.
• Predicted novel native pathways and proposed efficient heterologous pathways.

Conclusions:

• novoStoic enables the design of efficient lignin funneling pathways by exploring enzyme promiscuity.
• This approach can uncover new microbial pathways and optimize biotransformations for lignin valorization.
• The tool aids in developing carbon/energy-efficient processes using minimal heterologous enzymes.