Model-based biotechnological potential analysis of Kluyveromyces marxianus central metabolism

J Ind Microbiol Biotechnol. 2017 Aug;44(8):1177-1190. doi: 10.1007/s10295-017-1946-8. Epub 2017 Apr 25.

Abstract

The non-conventional yeast Kluyveromyces marxianus is an emerging industrial producer for many biotechnological processes. Here, we show the application of a biomass-linked stoichiometric model of central metabolism that is experimentally validated, and mass and charge balanced for assessing the carbon conversion efficiency of wild type and modified K. marxianus. Pairs of substrates (lactose, glucose, inulin, xylose) and products (ethanol, acetate, lactate, glycerol, ethyl acetate, succinate, glutamate, phenylethanol and phenylalanine) are examined by various modelling and optimisation methods. Our model reveals the organism's potential for industrial application and metabolic engineering. Modelling results imply that the aeration regime can be used as a tool to optimise product yield and flux distribution in K. marxianus. Also rebalancing NADH and NADPH utilisation can be used to improve the efficiency of substrate conversion. Xylose is identified as a biotechnologically promising substrate for K. marxianus.

Keywords: Central metabolism; Essentiality analysis; Kluyveromyces marxianus; Metabolic engineering; Modelling.

MeSH terms

  • Acetates / metabolism
  • Biomass
  • Calibration
  • Culture Media / chemistry
  • Ethanol / metabolism
  • Glucose / chemistry
  • Glutamic Acid / metabolism
  • Glycerol / metabolism
  • Industrial Microbiology*
  • Inulin / chemistry
  • Kluyveromyces / genetics
  • Kluyveromyces / metabolism*
  • Lactates / metabolism
  • Lactose / chemistry
  • Metabolic Engineering
  • Models, Molecular
  • Oxygen Consumption
  • Phenylalanine / metabolism
  • Phenylethyl Alcohol / metabolism
  • Reproducibility of Results
  • Succinic Acid / metabolism
  • Xylose / chemistry

Substances

  • Acetates
  • Culture Media
  • Lactates
  • Ethanol
  • Glutamic Acid
  • Phenylalanine
  • ethyl acetate
  • Inulin
  • Xylose
  • Succinic Acid
  • Glucose
  • Lactose
  • Phenylethyl Alcohol
  • Glycerol