Static Magnetic Field Increases Polyhydroxyalkanoates Biosynthesis in Haloferax mediterranei: Parameter Optimization and Mechanistic Insights from Metabolomics.

Polyhydroxyalkanoates (PHAs), as biosynthetic and biodegradable polymers, serve as alternatives to petroleum-based plastics, yet face critical cost barriers in large-scale production. While magnetic field (MF) stimulation enhances microbial activity, the optimal MF parameters and metabolic mechanisms for PHA biosynthesis remain unexplored. This study optimized magnetic field parameters to increase PHA biosynthesis in Haloferax mediterranei. A custom-engineered electromagnetic system identified 110 mT of static magnetic field (SMF) as the optimal level for biosynthesis, reaching 77.97 mg/(L·h) PHA volumetric productivity. A pulsed magnetic field caused oxidative stress and impaired substrate uptake despite increasing PHA synthesis. Prolonged SMF exposure (72 h) maximized PHA productivity, while 48 h of exposure attained 90% efficiency. Metabolomics revealed that SMF-driven carbon flux redirection via regulated butanoate metabolism led to a 2.10-fold increase in (R)-3-hydroxybutanoyl-CoA), while downregulating acetoacetate (0.51-fold) and suppressing PHA degradation (0.15-fold). This study pioneers the first application of metabolomics in archaea to decode SMF-induced metabolic rewiring in Haloferax mediterranei. Our findings establish SMF as a scalable bioenhancement tool, offering sustainable solutions for the circular bioeconomy.