Journal of Industrial Microbiology and Biotechnology

, Volume 22, Issue 1, pp 19-26

First online:

Commercial riboflavin production by recombinant Bacillus subtilis: down-stream processing and comparison of the composition of riboflavin produced by fermentation or chemical synthesis

  • W BretzelAffiliated withF Hoffmann-La Roche Ltd, Grenzacherstrasse 124, CH-4070 Basel, Switzerland
  • , W SchurterAffiliated withF Hoffmann-La Roche Ltd, Grenzacherstrasse 124, CH-4070 Basel, Switzerland
  • , B LudwigAffiliated withF Hoffmann-La Roche Ltd, Grenzacherstrasse 124, CH-4070 Basel, Switzerland
  • , E KupferAffiliated withF Hoffmann-La Roche Ltd, Grenzacherstrasse 124, CH-4070 Basel, Switzerland
  • , S DoswaldAffiliated withF Hoffmann-La Roche Ltd, Grenzacherstrasse 124, CH-4070 Basel, Switzerland
  • , M PfisterAffiliated withF Hoffmann-La Roche Ltd, Grenzacherstrasse 124, CH-4070 Basel, Switzerland
  • , A P G M van LoonAffiliated withF Hoffmann-La Roche Ltd, Grenzacherstrasse 124, CH-4070 Basel, Switzerland

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A novel process for riboflavin production using a recombinant Bacillus subtilis strain has been developed. Here we describe a down-stream processing procedure to obtain riboflavin qualities having a minimal content of 96% (‘feed-grade’) and 98% (‘food/pharma-grade’) riboflavin, respectively. Compared to riboflavin produced by chemical synthesis, products with improved chemical purity were obtained. All compounds representing more than 0.1% of the final products were identified. Feed-grade riboflavin material ex fermentation contained small amounts of amino acids and amino sugars and the biosynthetic riboflavin precursor dimethyl-ribityl-lumazine. All other side products found were derived from riboflavin, resulted from the purification procedure and were also found in riboflavin obtained by chemical synthesis. The Bacillus-produced riboflavin does not contain DNA. The data presented here were used to obtain product approval for the commercial application in the USA, Japan and the UK.

Keywords: recombinant Bacillus subtilis; riboflavin produced by fermentation; down-stream processing; analytics; registration