UV Mutagenesis Enhances DHA Biosynthesis in Schizochytrium sp. via Metabolic Reprogramming.

Schizochytrium sp., a marine alga prized for docosahexaenoic acid (DHA), was subjected to UV mutagenesis to boost industrial yields. The stable mutant UV1-3 achieved 5.01 g/L DHA-40.34% higher than wild-type S31. Transcriptomic and metabolomic analyses demonstrated that UV1-3 promotes docosahexaenoic acid (DHA) biosynthesis through coordinated metabolic regulation. Downregulation of key fatty acid synthase (FAS) pathway genes (ACSL, SLC27A2, FabI) reduced substrate competition for DHA precursors. Concurrently, RT-qPCR confirmed the upregulation of core polyketide synthase (PKS) pathway genes (orfA, orfB, orfC), directly enhancing DHA production. Furthermore, suppressed oxidative phosphorylation (evidenced by COX downregulation) and redirected carbon/nitrogen flux-achieved through diminished tricarboxylic acid (TCA) cycle activity (via downregulation of HAL and proC)-collectively favored DHA accumulation. These findings establish UV1-3 as a high-yielding industrial strain for DHA production and provide fundamental insights into metabolic flux regulation in Schizochytrium sp. These insights advance scalable, cost-effective microbial DHA production and deepen understanding of algal biosynthesis mechanisms, supporting sustainable omega-3 sourcing strategies.