title: [System metabolic engineering strategies for 2,3-butandione production by Torulopsis glabrata].
abstract: OBJECTIVE
  We regulated the carbon flux distribution of Torulopsis glabrata CCTCC M202019, an efficient pyruvate-producing microorganism, for improved 2, 3-butandione production.
  
  
  METHODS
  We overexpressed the acetolactate synthase (ALS) from Bacillus subtilis and then used the genome-scale metabolic model (GSMM) for T. glabrata (named iNX804) to evaluate the importance of deleting the ILV5 gene. In addition, the BDH gene was deleted to restrict the degradation of 2,3-butanedione.
  
  
  RESULTS
  Overexpression of the ALS resulted in a 4.6-fold increase in ALS activity and increased the extracellular concentration of 2,3-butanedione to 0.57 g/L from 0.01 g/L. The deletion of the ILV5 gene was found to increase the 2,3-butanedione accumulation level by 28.1%, attributed to the disruption of L-valine and L-leucine biosynthetic pathway. With the deletion of the BDH gene, the enzyme activity levels of butanedione reductase and butanediol dehydrogenase were decreased by 74.4% and 76.1%, respectively. And the accumulations of 3-hydroxybutanone and 2,3-butanediol were decreased by 52.2% and 71.4%, respectively. The final 2,3-butanedione concentration was 0.95 g/L, which was 30.1% higher than that of the control strain.
  
  
  CONCLUSIONS
  The GSMM based system metabolic engineering can be a functional strategy to redistribute the carbon flux from pyruvate node to 2,3-butanedione and achieve efficient accumulation of 2,3-butanedione.
authors.forename: Xiang
authors.initials: X
authors.lastname: Gao
authors.forename: Nan
authors.initials: N
authors.lastname: Xu
authors.forename: Shubo
authors.initials: S
authors.lastname: Li
authors.forename: Liming
authors.initials: L
authors.lastname: Liu
mesh_terms: D041221:Candida glabrata / Q000235:genetics / Q000378:metabolism*; D003931:Diacetyl / Q000378:metabolism*; D005285:Fermentation; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D060847:Metabolic Engineering / Q000379:methods*; D019289:Pyruvic Acid / Q000378:metabolism; D017384:Sequence Deletion
chemical_list: D005656:Fungal Proteins; D019289:Pyruvic Acid; D003931:Diacetyl