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.