# Native H2 pathways enable biocompatible hydrogenation of metabolic alkenes in bacteria

## TL;DR

This paper shows how bacteria can use their natural hydrogen pathways to perform chemical reactions in a sustainable and biocompatible way.

## Contribution

The novel approach combines native microbial H2 pathways with engineered alkene biosynthesis and membrane-bound Pd catalysis for in vivo hydrogenation.

## Key findings

- Genetically unmodified microorganisms can generate H2 in situ for alkene hydrogenation at the cell membrane.
- Hybrid chemo-microbial systems using waste feedstocks can achieve carbon-negative chemical synthesis.
- Membrane-bound Pd catalysts enable biocompatible transition metal catalysis in living cells.

## Abstract

Hydrogen gas is naturally produced by microorganisms from renewable feedstocks, yet industrial hydrogenation relies almost entirely on fossil fuel-derived H2. Despite advances in engineering biology and increasing demand for greener manufacturing, microbial H2 has seen limited application in chemical synthesis. Here we demonstrate that genetically unmodified microorganisms can generate H2 in situ to drive biocompatible alkene hydrogenation at the cell membrane using membrane-bound Pd catalysts. When combined with de novo alkene biosynthesis in engineered Escherichia coli, this system enables the simultaneous in vivo production of both substrate (alkene) and reagent (H2), followed by membrane-associated biohydrogenation to yield new metabolic end products. Quantitative life cycle assessment reveals that hybrid chemo-microbial systems utilizing waste feedstocks can outperform electrolytic hydrogenation and achieve carbon-negative outcomes. Together, this work demonstrates how microbial metabolites can be generated, intercepted and metabolically multiplexed to support biocompatible transition metal catalysis and sustainable chemical synthesis in living cells.

Most H2 used in the chemical industry is derived from fossil fuels. Now it has been shown that coupling native microbial H2 pathways with engineered alkene biosynthesis and membrane-bound Pd catalysis enables biocompatible hydrogenation of metabolic intermediates in living bacteria. This hybrid chemo-microbial platform supports the carbon-negative synthesis of industrial chemicals from waste-derived feedstocks.