Metabolic engineering strategies for neuroactive postbiotic production: Current progress and perspectives

Key Findings

The gut-brain axis (GBA) is a bidirectional communication network regulated in part by gut microbial metabolites that influence neurological, metabolic, and behavioral functions. Among these metabolites, neuroactive postbiotics such as γ-aminobutyric acid (GABA), short-chain fatty acids (SCFAs), serotonin, dopamine, and indole derivatives, have emerged as promising candidates for gut-brain modulation applications. Despite their therapeutic potential, industrial production of these compounds remains limited by low microbial productivity, pathway bottlenecks, and process instability. This review systematically examines recent advances in metabolic engineering and synthetic biology strategies for enhancing microbial biosynthesis of neuroactive postbiotics. Key approaches discussed include pathway optimization, regulatory element tuning, and cofactor balancing to achieve improved yields and stability. An emphasis is placed on the use of sustainable protein-rich feedstocks and agro-industrial byproducts as economical sources of amino acid precursors for large-scale fermentation. In addition, this review integrates Technology Readiness Level (TRL) assessment to evaluate the translational and industrial potential of neuroactive postbiotic production systems, thereby bridging laboratory-scale innovation with commercial implementation. Overall, this review highlights how the integration of metabolic engineering, synthetic biology, and sustainable bioprocessing can accelerate the development of next-generation neuroactive postbiotics for applications in functional foods, nutraceuticals, and neurotherapeutics.

Source

• Metabolic engineering strategies for neuroactive postbiotic production: Current progress and perspectives. — Journal of microbiological methods