title: Biotechnology of riboflavin.
abstract: Riboflavin (vitamin B2) production has shifted from chemical synthesis to exclusive biotechnological synthesis in less than 15 years. The underlying extraordinary achievement in metabolic engineering and bioprocess engineering is reviewed in this article with regard to the two most important industrial producers Bacillus subtilis and Ashbya gossypii. The respective biosynthetic routes and modifications are discussed, and also the regulation of riboflavin synthesis. As the terminal biosynthesis of riboflavin starts from the two precursors, ribulose 5-phosphate and guanosine triphosphate (GTP), both strains have been optimized for an improved flux through the pentose phosphate pathway as well as the purine biosynthetic pathway. Specific targets for improvement of A. gossypii were the increase of the glycine pool and the increase of carbon flow through the glyoxylic shunt. In B. subtilis, research interest, amongst others, has focused on gluconeogenesis and overexpression of the rib operon. In addition, insight into large-scale production of vitamin B2 is given, as well as future prospects and possible developments.
authors.affiliation: Institute of Systems Biotechnology, Saarland University, Campus A1.5, 66123, Saarbrücken, Germany.
authors.forename: Susanne Katharina
authors.initials: SK
authors.lastname: Schwechheimer
authors.affiliation: Laboratory of Biotechnology, Research Institute of Green Science and Technology, Shizuoka University, 836 Ohya Suruga-ku, Shizuoka, 422-8529, Japan.
authors.forename: Enoch Y
authors.initials: EY
authors.lastname: Park
authors.affiliation: Departamento de Microbiología y Genética, Metabolic Engineering Group, Universidad de Salamanca, Laboratory 323, Edificio Departamental, Campus Miguel de Unamuno, 37007, Salamanca, Spain.
authors.forename: José Luis
authors.initials: JL
authors.lastname: Revuelta
authors.affiliation: Institute of Systems Biotechnology, Saarland University, Campus A1.5, 66123, Saarbrücken, Germany.
authors.forename: Judith
authors.initials: J
authors.lastname: Becker
authors.affiliation: Institute of Systems Biotechnology, Saarland University, Campus A1.5, 66123, Saarbrücken, Germany. christoph.wittmann@uni-saarland.de.
authors.forename: Christoph
authors.initials: C
authors.lastname: Wittmann
mesh_terms: D001412:Bacillus subtilis / Q000235:genetics / Q000378:metabolism*; D053898:Biosynthetic Pathways / Q000235:genetics*; D001709:Biotechnology / Q000379:methods*; D055169:Eremothecium / Q000235:genetics / Q000378:metabolism*; D060847:Metabolic Engineering / Q000379:methods*; D012256:Riboflavin / Q000096:biosynthesis*
chemical_list: D012256:Riboflavin
keywords: Ashbya gossypii; Bacillus subtilis; Metabolic engineering; Riboflavin; Vitamin B2