Enhancing Bacterial Secondary Metabolite Yields Using Non-Biological Inducers: Blind metabolic engineering

Abstract Bacteria secondary metabolites are widely used in many industries, including pharmaceutical, food, agricultural, and cosmetics. Abiotic stresses are a low-cost and easy approach to enhance the accumulation of these metabolites. On the other hand, rational metabolic engineering strategies are limited by the unknown metabolic burden, incomplete pathway knowledge, and biosafety concerns associated with genetically modified microorganisms (GMMs). This review surveys abiotic stress–driven strategies to boost secondary metabolite production in bacterial strains. It systematically analyzes how key abiotic stress—osmotic, oxidative, pH, solvent, and radiation—reshape microbial metabolism and secondary metabolite biosynthetic pathways. The main idea of this review is to elucidate the interconnected network linking diverse stress stimuli to bacterial molecular defense mechanisms, and to explore the potential applications of this crosstalk in the rational design of metabolic engineering approaches. According to the collected evidences from various studies, abiotic stresses are able to induce a significant enhancement in the production of a wide-range of secondary metabolites including pigments, fatty acids, enzymes, antibiotics, organic acids, amino acids, and alcohols in the industrially-important bacterial strains. This review emphasizes that response to abiotic stresses is significantly strain-depended and metabolite-depended, which highlights the necessity of customization of stress regimens toward specific strains and secondary metabolites.