Synergistic experimental and computational approach identifies novel strategies for polyhydroxybutyrate overproduction

Adil Alsiyabi, Brandi Brown, Cheryl Immethun, Dianna Long, Mark Wilkins, Rajib Saha

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


Polyhydroxybutyrate (PHB) is a sustainable bioplastic produced by bacteria that is a potential replacement for conventional plastics. This study delivers an integrated experimental and computational modeling approach to decipher metabolic factors controlling PHB production and offers engineering design strategies to boost production. In the metabolically robust Rhodopseudomonas palustris CGA009, PHB production significantly increased when grown on the carbon- and electron-rich lignin breakdown product p-coumarate (C9H8O3) compared to virtually no PHB titer from acetate (C2H3NaO2). The maximum yield did not improve further when grown on coniferyl alcohol (C10H12O3), but comparison of the PHB profiles showed that coniferyl alcohol's higher carbon content resulted in a higher rate of PHB production. Combined experimental results revealed that cytoplasmic space may be a limiting factor for maximum PHB titer. In order to obtain a systems-level understanding of factors driving PHB yield, a model-driven investigation was performed. The model yielded several engineering design strategies including utilizing reduced, high molecular weight substrates that bypass the thiolase reaction (phaA). Based on these strategies, utilization of butyrate was predicted and subsequently validated to produce PHB. Model analysis also explained why nitrogen starvation was not essential for PHB production and revealed that renewable and abundant lignin aromatics are ideal candidates for PHB production. Most importantly, the generality of the derived design rules allows them to be applied to any PHB-producing microbe with similar metabolic features.

Original languageEnglish (US)
Pages (from-to)1-13
Number of pages13
JournalMetabolic Engineering
StatePublished - Nov 2021


  • Bioplastics
  • Lignin
  • Metabolic modeling
  • Polyhydroxyalkanoates

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology


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