Metabolic flux analysis for biosynthesis of poly(β-Hydroxybutyric Acid) in alcaligenes eutrophus from various carbon sources

Huidong Shi, Masafumi Shiraishi, Kazuyuki Shimizu

Research output: Contribution to journalArticlepeer-review

91 Scopus citations


Using the available biochemical information, metabolic networks have been constructed to describe the biochemistry of synthesis of poly-/S-hydroxybutyrate (PHB) in Akaligenes eutrophus on a variety of carbon substrates. A metabolic flux analysis of PHB biosynthesis under nitrogen limited conditions was made using butyrate, lactate and acetate as carbon sources. Although the substrates share most metabolic pathways, their flux distributions are quite different. In the case with butyrate as the carbon source, a nearly constant flux of TCA cycle through isocitrate dehydrogenase under both balanced growth and nitrogen limiting conditions was obtained from the flux computation. The carbon flow was determined to proceed alternatively through the glyoxylate pathway or the PHB synthetic pathway according to the availability of a nitrogen source. A block in the amino acid synthetic pathway may result in the overproduction of NADPH and accelerate the biosynthesis of PHB. Flux ratios allow a comparison of the effects of carbon sources on PHB synthesis. The results demonstrate that butyrate is more efficient than acetate and lactate for PHB production from an energetic point of view. The metabolic networks constructed were also applied to perform a theoretical analysis on the overproduction of PHB. The results indicate that the maximum PHB yield may be limited by the available NADPH.

Original languageEnglish (US)
Pages (from-to)579-587
Number of pages9
JournalJournal of Fermentation and Bioengineering
Issue number6
StatePublished - 1997
Externally publishedYes


  • Alcaligenes eutrophus
  • Flux analysis
  • Metabolic engineering
  • Phb biosynthesis

ASJC Scopus subject areas

  • Biotechnology
  • Applied Microbiology and Biotechnology


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