Genomic and Transcriptomic Characterization of a High-Yield Docosahexaenoic Acid (DHA) Mutant Schizochytrium sp. HS01

Docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid essential for human health, is primarily produced at scale using Schizochytrium sp. Mutagenesis-based strain improvement has increased DHA yields, but the genetic and metabolic mechanisms underlying high productivity remain poorly understood. Here, we conducted the comparative whole-genome sequencing and transcriptomic profiling of a high-DHA-yielding mutant strain (HS01) and its parental strain (GS00). The GS00 genome assembly spans 62.4 Mb and encodes 14,886 predicted genes. Functional annotation highlighted pathways involved in central metabolism, saturated fatty acid (SFA) synthesis, and polyunsaturated fatty acid (PUFA)/DHA biosynthesis. Comparative genomics identified 40 insertions/deletions and 396 single-nucleotide polymorphisms between HS01 and GS00, including mutations in the coding and regulatory regions of key metabolic genes. Transcriptomic analysis revealed extensive metabolic reprogramming in HS01, including the upregulation of glycolysis and tricarboxylic acid (TCA) cycle genes, along with a distinct fatty acid profile and the altered expression of fatty acid metabolism genes compared with GS00. Collectively, the integrated genomic and transcriptomic analyses not only pinpointed specific mutations potentially associated with the HS01 high-DHA phenotype but also revealed substantial transcriptional and metabolic remodeling, providing valuable insights into the mechanisms that drive enhanced DHA biosynthesis.