Three biotechnical processes using Ashbya gossypii, Candida famata, or Bacillus subtilis compete with chemical riboflavin production

Chemical riboflavin production, successfully used for decades, is in the co urse of being replaced by microbial processes. These promise to save half t he costs, reduce waste and energy requirements, and use renewable resources like sugar or plant oil. Three microorganisms are currently in use for ind ustrial riboflavin production. The hemiascomycetes Ashbya gossypii, a filam entous fungus, and Candida famata, a yeast, are naturally occurring overpro ducers of this vitamin. To obtain riboflavin production with the Gram-posit ive bacterium Bacillus subtilis requires at least the deregulation of purin e synthesis and a mutation in a flavokinase/FAD-synthetase. It is common to all three organisms that riboflavin production is recognizable by the yell ow color of the colonies. This is an important tool for the screening of im proved mutants. Antimetabolites like itaconate, which inhibits the isocitra te lyase in A. gossypii, tubercidin, which inhibits purine biosynthesis in C. famata, or roseoflavin, a structural analog of riboflavin used for B. su btilis, have been applied successfully for mutant selections. The productio n of riboflavin by the two fungi seems to be limited by precursor supply, a s was concluded from feeding and gene-overexpression experiments. Although Aux studies in B. subtilis revealed an increase both in maintenance metabol ism and in the oxidative part of the pentose phosphate pathway, the major l imitation there seems to be the riboflavin pathway. Multiple copies of the rib genes and promoter replacements are necessary to achieve competitive pr oductivity.