Metabolic modeling of polyhydroxybutyrate biosynthesis

Timothy A. Leaf, Friedrich Srienc

Research output: Contribution to journalArticlepeer-review

59 Scopus citations

Abstract

A mathematical model describing intracellular polyhydroxybutyrate (PHB) synthesis in Alcaligenes eutrophus has been constructed. The model allows investigation of issues such as the existence of rate-limiting enzymatic steps, possible regulatory mechanisms in PHB synthesis, and the effects different types of rate expressions have on model behavior. Simulations with the model indicate that activities of all PHB pathway enzymes influence overall PHB flux and that no single enzymatic step can easily be identified as rate limiting. Simulations also support regulatory roles for both thiolase and reductase, mediated through AcCoA/CoASH and NADPH/NADP+ ratios, respectively. To make the model more realistic, complex rate expressions for enzyme-catalyzed reactions were used which reflect both the reversibility of the reactions and the reaction mechanisms. Use of the complex kinetic expressions dramatically changed the behavior of the system compared to a simple model containing only Michaelis-Menten kinetic expressions; the more complicated model displayed different responses to changes in enzyme activities as well as inhibition of flux by the reaction products CoASH and NADP+. These effects can be attributed to reversible rate expressions, which allow prediction of reaction rates under conditions both near and far from equilibrium.

Original languageEnglish (US)
Pages (from-to)557-570
Number of pages14
JournalBiotechnology and bioengineering
Volume57
Issue number5
DOIs
StatePublished - Mar 5 1998

Keywords

  • Alcaligenes eutrophus
  • Enzyme kinetics
  • Mathematical modeling
  • Metabolic engineering
  • Polyhydroxyalkanoates
  • Regulation of metabolism

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