Abstract
Although microparticle-enhanced cultivation (MPEC) significantly improves transglutaminase (TGase) yield, its underlying mechanism remains unclear. This study elucidated how talc and CaCO(3) boost TGase production in Streptomyces mobaraensis HVCP-Sm1. Transcriptomic analysis revealed that both microparticles reprogram energy metabolism, but through distinct pathways: talc primarily enhanced energy conversion efficiency by activating ATP synthase and proton transmembrane transport, while CaCO(3) augmented the supply of ATP and the substrate glutamine. Furthermore, overexpression of XDH-D (Gene 5232), encoding xanthine dehydrogenase subunit D, increased TGase titer by 39.4% to 21.24 U/mL. These findings demonstrate that talc and CaCO(3) promote TGase synthesis by differentially rewiring central energy metabolism, and highlight the critical role of energy metabolic regulation in Streptomyces secondary metabolism. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s42770-026-01921-z.