Theoretically possible yields of microbial secondary products

Area of Science:

• Biochemistry
• Metabolic Engineering
• Systems Biology

Background:

• Secondary metabolites are crucial in various biological processes and industrial applications.
• Understanding the efficiency of their biosynthesis is key to optimizing production.
• Primary metabolism provides essential building blocks and energy for cellular functions.

Purpose of the Study:

• To formulate balance equations for major secondary metabolite biogenetic groups.
• To calculate theoretical maximum yields (Yp/s max) for these metabolites from glucose.
• To compare the biosynthetic efficiency of secondary metabolism with primary metabolism.

Main Methods:

• Formulation of stoichiometric balance equations for known and probable biosynthetic pathways.
• Calculation of maximum product yield coefficients (Yp/s max) based on glucose as the substrate.
• Integration of Yp/s max values into substrate consumption models.

Main Results:

• Calculated Yp/s max values ranged from 0.37 to 0.9, aligning with theoretical yields of cell dry mass components.
• Sugar derivatives, beta-lactams, shikimate derivatives, polyketides, and mevalonate derivatives were stoichiometrically linked to carbohydrates, proteins, and lipids, respectively.
• Secondary metabolism exhibited similar biosynthetic efficiency to primary metabolism under retarded growth conditions.

Conclusions:

• Stoichiometric analysis suggests comparable efficiency between secondary and primary metabolism for product formation.
• A significant portion (>70%) of glucose is channeled into byproducts or waste metabolites.
• Metabolic engineering strategies may be needed to redirect carbon flux towards desired secondary metabolites and reduce waste.