Prospecting Biochemical Pathways to Implement Microbe-Based Production of the New-to-Nature Platform Chemical...

Area of Science:

• Synthetic biology and metabolic engineering
• Biotechnology and industrial microbiology
• Chemical synthesis and biocatalysis

Background:

• Levulinic acid is a key platform chemical with broad industrial applications.
• Current microbial biosynthetic pathways for levulinic acid are unknown, hindering sustainable production.
• Synthetic biology enables the creation of novel biosynthetic pathways using new enzyme combinations.

Purpose of the Study:

• To computationally identify and evaluate candidate biosynthetic pathways for levulinic acid production in *Escherichia coli* and *Saccharomyces cerevisiae*.
• To leverage synthetic biology for the development of new-to-nature pathways for sustainable chemical manufacturing.

Main Methods:

• Computational screening of hundreds of enzyme combinations for novel biosynthetic pathways.
• Manual curation and selection of promising candidate pathways.
• Genome-scale metabolic modeling to assess pathway performance and identify bottlenecks in *E. coli* and *S. cerevisiae*.

Main Results:

• Five high-potential biosynthetic pathways for levulinic acid production were identified.
• Computational modeling predicted pathway performance and potential limitations in the selected microbial hosts.
• The study demonstrates a systematic approach for designing new-to-nature biosynthetic pathways.

Conclusions:

• The developed computational framework facilitates the design of microbial systems for producing levulinic acid.
• This research provides a strategy for implementing novel biosynthetic pathways for various value-added chemicals.
• The findings support the advancement of synthetic industrial microbiotechnology for sustainable chemical production.