Computationally-aided and polyketide synthase-based controlled synthesis of polycyclopropanated fuel molecules

ABSTRACT: Reducing carbon emissions from aviation and other long-distance transportation sectors requires the development of sustainable biofuels with suitable energy density, freezing point, and other physical properties. We previously demonstrated heterologous production of high energy polycyclopropanated fatty acids (POP-FAs, class I) using an iterative polyketide synthase (iPKS) pathway in a Streptomyces host. This pathway naturally incorporates multiple cyclopropane rings in a manner that is challenging to replicate with organic synthesis. However, to engineer biosynthesis towards specific desired POP-FA molecules, the product programming mechanisms for this iterative pathway must be understood. Here we present a strategy to modify the chain length and cyclopropane ratio of POP-FAs by in vivo gene exchange. Guided by phylogenetic and structural analysis, we identify the POP cyclopropanase (CP) gene to be a key target for POP diversification and engineering. Then, leveraging both natural and engineered pathway product diversity, we demonstrate targeted production of new classes of POP-FAs, namely medium-chain POP-FAs (class II) with distinct cyclopropane positions, as well as fully cyclopropane-saturated POP-FAs (class III) by chimeric POP iPKS pathways in Streptomyces. Compared to class I POP-FAs, class II POP-FAs have superior freezing point properties for aviation, while class III POP-FAs present an energy-density improvement for rocketry. These precise and controllable modifications to POP-FA structure open the door for bioproduction of designer POP fuels.

INSTRUMENT(S):

ORGANISM(S): Streptomyces Albus Group Streptomyces Coelicolor

SUBMITTER: Christopher Petzold  

LAB HEAD: Christopher J. Petzold

PROVIDER: PXD057441 | Pride | 2026-03-05

REPOSITORIES: Pride