Suppression of lactate production by aerobic fed-batch cultures of Lactococcus lactis

J Biosci Bioeng. 2020 Oct;130(4):402-408. doi: 10.1016/j.jbiosc.2020.06.004. Epub 2020 Jul 12.

Abstract

Aerobic fed-batch cultures were studied as a means of suppressing the production of lactate, which inhibits the growth of lactic acid bacteria (LAB). LAB produce lactate via lactate dehydrogenase (LDH), regenerating nicotinamide adenine dinucleotide (NAD+) consumed during glycolysis. Therefore, we focused on NADH oxidase (NOX), employing oxygen as an electron acceptor, as an alternative pathway to LDH for NAD+ regeneration. To avoid glucose repression of NOX and NAD+ consumption by glycolysis exceeding NAD+ regeneration by NOX, glucose was fed gradually. When Lactococcus lactis MG 1363 was aerobically fed at a specific growth rate of 0.2 h-1, the amount of lactate produced per amount of grown cell was reduced to 12% of that in anaerobic batch cultures. Metabolic flux analysis revealed that in addition to NAD+ regeneration by NOX, ATP acquisition by production of acetate and NAD+ regeneration by production of acetoin and 2,3-butanediol contributed to suppression of lactate production.

Keywords: Aerobic; Fed-batch culture; Flux analysis; Glucose repression; Lactic acid bacteria; NADH oxidase.

MeSH terms

  • Aerobiosis
  • Batch Cell Culture Techniques*
  • Glucose / metabolism
  • Glycolysis
  • L-Lactate Dehydrogenase / metabolism
  • Lactic Acid / biosynthesis*
  • Lactococcus lactis / growth & development*
  • Lactococcus lactis / metabolism*
  • Multienzyme Complexes / metabolism
  • NAD / metabolism
  • NADH, NADPH Oxidoreductases / metabolism

Substances

  • Multienzyme Complexes
  • NAD
  • Lactic Acid
  • L-Lactate Dehydrogenase
  • NADH oxidase
  • NADH, NADPH Oxidoreductases
  • Glucose