Systems biology approach identifies functional modules and regulatory hubs related to secondary metabolites accumulation after the transition from autotrophic to heterotrophic growth condition in the microalga

Heterotrophic cultures are among the most promising strategies put forth to overcome the low biomass and secondary metabolites productivity challenge. To shedding light on the underlying molecular mechanisms, weighted gene co-expression network analysis (WGCNA) was integrated with transcriptome meta-analysis, connectivity analysis, functional enrichment, and hub genes identification. Meta-analysis and Functional enrichment analysis demonstrated that with the progress to developmental phases at heterotrophic growth condition, most of the biological processes are up-regulated, which leads to the change of genetic architectures and phenotypic outcomes. WGNCA analysis of meta-genes also created four significant functional modules across logarithmic (LG), transition (TR), and production peak (PR) phases. The expression pattern and connectivity characteristics of the brown module as a non-preserved module vary across LG, TR, and PR phases. Functionally analysis identified “Carotenoid biosynthesis”, “Fatty acid metabolism”, and “Methane metabolism” as enriched pathways in the non-preserved module. Moreover, the integrated approach was applied here, identified some hub genes, such as serine hydroxymethyltransferase (SHMT1) for development of metabolites accumulating strains in microalgae. Our study provided a new insight into underlying mechanisms of metabolite accumulation and opens new avenue for the future applied studies in the microalgae field.