Blockage of the pyrimidine biosynthetic pathway affects riboflavin production in Ashbya gossypii

• Riboflavin overproduction by A. gossypii Agura3 on standard complex medium.
• Excess uridine/uracil repressed the production of riboflavin by this auxotroph.
• High uracil concentrations were detrimental for the A. gossypii growth.
• Excess uridine favored the A. gossypii Agura3 growth.
• Alterations in the A. gossypii pyrimidine pathway affected riboflavin production.

The Ashbya gossypii riboflavin biosynthetic pathway and its connection with the purine pathway have been well studied. However, the outcome of genetic alterations in the pyrimidine pathway on riboflavin production by A. gossypii had not yet been assessed. Here, we report that the blockage of the de novo pyrimidine biosynthetic pathway in the recently generated A. gossypii Agura3 uridine/uracil auxotrophic strain led to improved riboflavin production on standard agar-solidified complex medium. When extra uridine/uracil was supplied, the production of riboflavin by this auxotroph was repressed. High concentrations of uracil hampered this (and the parent) strain growth, whereas excess uridine favored the A. gossypii Agura3 growth. Considering that the riboflavin and the pyrimidine pathways share the same precursors and that riboflavin overproduction may be triggered by nutritional stress, we suggest that overproduction of riboflavin by the A. gossypii Agura3 may occur as an outcome of a nutritional stress response and/or of an increased availability in precursors for riboflavin biosynthesis, due to their reduced consumption by the pyrimidine pathway.