title: Comparative metabolic flux analysis of an Ashbya gossypii wild type strain and a high riboflavin-producing mutant strain.
abstract: In the present study, we analyzed the central metabolic pathway of an Ashbya gossypii wild type strain and a riboflavin over-producing mutant strain developed in a previous study in order to characterize the riboflavin over-production pathway. (13)C-Metabolic flux analysis ((13)C-MFA) was carried out in both strains, and the resulting data were fit to a steady-state flux isotopomer model using OpenFLUX. Flux to pentose-5-phosphate (P5P) via the pentose phosphate pathway (PPP) was 9% higher in the mutant strain compared to the wild type strain. The flux from purine synthesis to riboflavin in the mutant strain was 1.6%, while that of the wild type strain was only 0.1%, a 16-fold difference. In addition, the flux from the cytoplasmic pyruvate pool to the extracellular metabolites, pyruvate, lactate, and alanine, was 2-fold higher in the mutant strain compared to the wild type strain. This result demonstrates that increased guanosine triphosphate (GTP) flux through the PPP and purine synthesis pathway (PSP) increased riboflavin production in the mutant strain. The present study provides the first insight into metabolic flux through the central carbon pathway in A. gossypii and sets the foundation for development of a quantitative and functional model of the A. gossypii metabolic network.
authors.affiliation: Laboratory of Biotechnology, Integrated Bioscience Section, Graduate School of Science and Technology, Shizuoka University, 836 Ohya Suruga-ku, Shizuoka 422-8529, Japan. Electronic address: samsuni11@hotmail.com.
authors.forename: Bo-Young
authors.initials: BY
authors.lastname: Jeong
authors.affiliation: Institute of Biochemical Engineering, Braunschweig University of Technology, Gauss Street 17, Braunschweig 38106, Germany. Electronic address: c.wittmann@tu-braunschweig.de.
authors.forename: Christoph
authors.initials: C
authors.lastname: Wittmann
authors.affiliation: Research Institute of Green Science and Technology, Shizuoka University, 836 Ohya Suruga-ku, Shizuoka 422-8529, Japan. Electronic address: atkato@ipc.shizuoka.ac.jp.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kato
authors.affiliation: Laboratory of Biotechnology, Integrated Bioscience Section, Graduate School of Science and Technology, Shizuoka University, 836 Ohya Suruga-ku, Shizuoka 422-8529, Japan; Research Institute of Green Science and Technology, Shizuoka University, 836 Ohya Suruga-ku, Shizuoka 422-8529, Japan. Electronic address: acypark@ipc.shizuoka.ac.jp.
authors.forename: Enoch Y
authors.initials: EY
authors.lastname: Park
mesh_terms: D002244:Carbon / Q000378:metabolism; D055169:Eremothecium / Q000235:genetics* / Q000378:metabolism*; D064688:Metabolic Flux Analysis; D009154:Mutation / Q000235:genetics*; D011687:Purines / Q000096:biosynthesis; D012256:Riboflavin / Q000096:biosynthesis*
chemical_list: D011687:Purines; D002244:Carbon; D012256:Riboflavin; C030985:purine
keywords: (13)C metabolic flux analysis; Ashbya gossypii; Central carbon metabolism; Mutant; Riboflavin