Evolutionary flexibility and rigidity in the bacterial methylerythritol phosphate (MEP) pathway

Area of Science:

• Metabolic Engineering
• Synthetic Biology
• Microbial Biotechnology

Background:

• Terpenoids are vital compounds used in industry, pharmaceuticals, and fragrances.
• Current industrial terpenoid production relies on nonrenewable resources, driving efforts for sustainable microbial fermentation.
• The methylerythritol phosphate (MEP) pathway is key for terpenoid precursor synthesis, involving enzymes Dxs, IspG, and IspH.

Purpose of the Study:

• To investigate the evolutionary diversity of terpenoid biosynthesis pathways.
• To identify potential alternative enzymes or pathways to overcome limitations in microbial terpenoid production.
• To inform metabolic engineering strategies for sustainable terpenoid biosynthesis.

Main Methods:

• Comparative genomics analysis of 4,400 diverse bacterial species.
• Surveying genomic data for alternative enzymatic routes in terpenoid biosynthesis.
• Evaluating the evolutionary flexibility and rigidity of key MEP pathway enzymes.

Main Results:

• Identified evolutionary flexibility in the Dxs enzyme of the MEP pathway, with some species possessing alternatives.
• Found evolutionary rigidity in IspG and IspH enzymes, with no identified species circumventing these essential iron-sulfur cluster enzymes.
• Highlighted the indispensability of IspG and IspH for terpenoid biosynthesis across surveyed bacterial species.

Conclusions:

• Enzymes IspG and IspH are evolutionarily indispensable, posing a challenge for metabolic engineering of terpenoid biosynthesis.
• The study provides insights into the evolution of terpenoid biosynthesis pathways.
• Leveraging genomic data can uncover alternative metabolic solutions for sustainable chemical production.