Increased riboflavin production by manipulation of inosine 5-monophosphate dehydrogenase in Ashbya gossypii

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• 作者：Rubén M. Buey ; Rodrigo Ledesma-Amaro…
• 关键词：Ashbya gossypii ; Metabolic engineering ; Riboflavin ; Inosine 5-monophosphate dehydrogenase
• 刊名：Applied Microbiology and Biotechnology
• 出版年：2015
• 出版时间：November 2015
• 年：2015
• 卷：99
• 期：22
• 页码：9577-9589
• 全文大小：2,141 KB
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• 作者单位：Rubén M. Buey (1)
  Rodrigo Ledesma-Amaro
  Mónica Balsera (2)
  José María de Pereda (3)
  José Luis Revuelta (1)
  
  1. Metabolic Engineering Group, Departamento de Microbiología y Genética, Universidad de Salamanca, Edificio Departamental, Campus Miguel de Unamuno, 37007, Salamanca, Spain
  2. Department Abiotic Stress, Instituto de Recursos Naturales y Agrobiología, Consejo Superior de Investigaciones Científicas, C/ Cordel de Merinas 40-52, 37008, Salamanca, Spain
  3. Instituto de Biología Celular y Molecular del Cáncer, Consejo Superior de Investigaciones Científicas, Universidad de Salamanca, Campus Miguel de Unamuno, 37007, Salamanca, Spain
  
• 刊物类别：Chemistry and Materials Science
• 刊物主题：Chemistry
  Biotechnology
  Microbiology
  Microbial Genetics and Genomics
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1432-0614

文摘

Guanine nucleotides are the precursors of essential biomolecules including nucleic acids and vitamins such as riboflavin. The enzyme inosine-5-monophosphate dehydrogenase (IMPDH) catalyzes the ratelimiting step in the guanine nucleotide de novo biosynthetic pathway and plays a key role in controlling the cellular nucleotide pools. Thus, IMPDH is an important metabolic bottleneck in the guanine nucleotide synthesis, susceptible of manipulation by means of metabolic engineering approaches. Herein, we report the functional and structural characterization of the IMPDH enzyme from the industrial fungus Ashbya gossypii. Our data show that the overexpression of the IMPDH gene increases the metabolic flux through the guanine pathway and ultimately enhances 40 % riboflavin production with respect to the wild type. Also, IMPDH disruption results in a 100-fold increase of inosine excretion to the culture media. Our results contribute to the developing metabolic engineering toolbox aiming at improving the production of metabolites with biotechnological interest in A. gossypii. Keywords Ashbya gossypii Metabolic engineering Riboflavin Inosine 5-monophosphate dehydrogenase