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<p>Reducing carbon emissions from aviation and long-distance transportation sectors requires the development of sustainable biofuels with suitable energy density, freezing point, and other physical properties. We previously demonstrated biological production of high energy polycyclopropanated fatty acids (POP-FAs, class I) using an iterative polyketide synthase (iPKS) pathway in a <i>Streptomyces</i> host. Here, we used a computational model of fuel properties to identify chain length and cyclopropanation control as critical steps to engineer this iPKS for biofuel applications. We next explored the natural diversity of POP biosynthesis by investigating homologous pathways. Then, by in vivo gene exchange, we determined cyclopropanase (CP) catalysis to be key for POP-FA engineering. Leveraging both natural and engineered pathway product diversity, we demonstrate targeted production of improved POP-FAs, namely shortened POP-FAs with predicted superior freezing point properties for aviation, as well as fully cyclopropane-saturated POP-FAs which should have superior energy-density. These precise and controllable modifications to POP-FA structure open the door for bioproduction of designer POP fuels.</p>

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Polyketide synthase-based controlled synthesis of polycyclopropanated fuel molecules

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年5月27日

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  • Kevin Yin,
  • Alexander Landera,
  • Namil Lee,
  • Anthony T. Iavarone,
  • Suzanne M. Kosina,
  • Thomas D. Young,
  • Kai Deng,
  • Justin Baerwald,
  • Yan Chen,
  • Jennifer W. Gin,
  • Riley Benedict,
  • Yan Chiu,
  • Ezechinyere Ukabiala,
  • Methun Kamruzzaman,
  • Kunal Poorey,
  • Trent R. Northen,
  • Christopher J. Petzold,
  • Anthe George,
  • Pablo Cruz-Morales,
  • Qingyun Dan,
  • Jay D. Keasling

摘要

Reducing carbon emissions from aviation and long-distance transportation sectors requires the development of sustainable biofuels with suitable energy density, freezing point, and other physical properties. We previously demonstrated biological production of high energy polycyclopropanated fatty acids (POP-FAs, class I) using an iterative polyketide synthase (iPKS) pathway in a Streptomyces host. Here, we used a computational model of fuel properties to identify chain length and cyclopropanation control as critical steps to engineer this iPKS for biofuel applications. We next explored the natural diversity of POP biosynthesis by investigating homologous pathways. Then, by in vivo gene exchange, we determined cyclopropanase (CP) catalysis to be key for POP-FA engineering. Leveraging both natural and engineered pathway product diversity, we demonstrate targeted production of improved POP-FAs, namely shortened POP-FAs with predicted superior freezing point properties for aviation, as well as fully cyclopropane-saturated POP-FAs which should have superior energy-density. These precise and controllable modifications to POP-FA structure open the door for bioproduction of designer POP fuels.