Discovery and analysis of novel metabolic pathways for the biosynthesis of industrial chemicals: 3-hydroxypropanoate

Christopher S. Henry, Linda J Broadbelt, Vassily Hatzimanikatis*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

117 Scopus citations

Abstract

Sustainable microbial production of high-value organic compounds such as 3-hydroxypropanoate (3HP) is becoming an increasingly attractive alternative to organic syntheses that utilize petrochemical feedstocks. We applied the Biochemical Network Integrated Computational Explorer (BNICE) framework to the automated design and evaluation of novel biosynthetic routes for the production of 3HP from pyruvate. Among the pathways generated by the BNICE framework were all of the known pathways for the production of 3HP as well as numerous novel pathways. The pathways generated by BNICE were ranked based on four criteria: pathway length, thermodynamic feasibility, maximum achievable yield to 3HP from glucose, and maximum achievable activity at which 3HP can be produced. Four pathways emerged from this ranking as the most promising for the biosynthesis of 3HP, and three of these pathways, including the shortest pathways discovered, were novel. We also discovered novel routes for the biosynthesis of 28 commercially available compounds that are currently produced exclusively through organic synthesis. Examination of the optimal pathways for the biosynthesis of these 28 compounds in E. coli revealed pyruvate and succinate to be ideal intermediates for achieving high product yields from glucose.

Original languageEnglish (US)
Pages (from-to)462-473
Number of pages12
JournalBiotechnology and Bioengineering
Volume106
Issue number3
DOIs
StatePublished - Jun 15 2010

Keywords

  • Automated pathway generation
  • BNICE
  • Escherichia coli
  • Flux balance analysis
  • TMFA
  • Thermodynamic feasibility

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology

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