Polyketide synthase-based controlled synthesis of polycyclopropanated fuel molecules
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.
Authors
- Methun Kamruzzaman (ORCID: https://orcid.org/0000-0002-8680-7061)
- Thomas D. Young (ORCID: https://orcid.org/0000-0002-3234-7418)
- Anthe George (ORCID: https://orcid.org/0000-0003-1583-3972)
- Anthony T. Iavarone
- Suzanne M. Kosina (ORCID: https://orcid.org/0000-0003-2885-1248)
- Namil Lee (ORCID: https://orcid.org/0009-0000-0382-8741)
- Trent R. Northen (ORCID: https://orcid.org/0000-0001-8404-3259)
- Kai Deng (ORCID: https://orcid.org/0000-0002-9973-8130)
- Qingyun Dan (ORCID: https://orcid.org/0000-0002-3110-9450)
- Kevin Yin (ORCID: https://orcid.org/0000-0002-3639-1125)
- Y Chen
- Alexander Landera (ORCID: https://orcid.org/0000-0002-5314-9357)
- Kunal Poorey (ORCID: https://orcid.org/0000-0003-3665-0235)
- R Benedict
- Ezechinyere Ukabiala
- Yan Chiu
- Jay D. Keasling (ORCID: https://orcid.org/0000-0003-4170-6088)
- Pablo Cruz-Morales (ORCID: https://orcid.org/0000-0002-6751-8897)
- Justin Baerwald
- Jennifer W. Gin
- Christopher J. Petzold (ORCID: https://orcid.org/0000-0002-8270-5228)
Institutions
- QB3 (US)
- Lawrence Berkeley National Laboratory (US)
- Korea Advanced Institute of Science and Technology (KR)
- University of California, San Francisco (US)
- Sandia National Laboratories California (US)
- Novo Nordisk Foundation (DK)
- Novo Nordisk (Germany) (DE)
- Joint BioEnergy Institute (US)
- University of California, Berkeley (US)
- Technical University of Denmark (DK)
Publication Details
- Journal
- Nature Communications
- Published
- 2026-05-27
- DOI
- https://doi.org/10.1038/s41467-026-73172-3
- Primary Topic
- Cyclopropane Reaction Mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- U.S. Department of Energy
- Novo Nordisk
- Novo Nordisk Fonden
- Office of Science
- National Nuclear Security Administration
- Biological and Environmental Research
- Laboratory Directed Research and Development
- Sandia National Laboratories
- Lawrence Berkeley National Laboratory