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

Abstract

Heterotrophic growth mode is 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, transcriptome meta-analysis was integrated with weighted gene co-expression network analysis (WGCNA), connectivity analysis, functional enrichment, and hubs identification. Meta-analysis and Functional enrichment analysis demonstrated that most of the biological processes are up-regulated at heterotrophic growth condition, which leads to change of genetic architectures and phenotypic outcomes. WGNCA analysis of meta-genes also resulted 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. Functional analysis identified Carotenoid biosynthesis, Fatty acid metabolism and Methane metabolism as enriched pathways in the non-preserved module. Our integrated approach was applied here, identified some hubs, such as a serine hydroxymethyltransferase (SHMT1), which is the best candidate for development of metabolites accumulating strains in microalgae. Current study provided a new insight into underlying metabolite accumulation mechanisms and opens new avenue for the future applied studies in the microalgae field.

Fig 1. Flow chart of applied systems biology approach in current study.

Fig 2

Identified meta genes in two data sets at logarithmic (A), transition (B) and production peak (C) phases after the transition from autotrophic to heterotrophic growth mode.

Fig 3. Distribution of TFs, TRs, and PKs families identified in meta genes.

The number TF families (A, B and C), TRs families (D, E, and F), PKs families (G, H, and I) in meta genes at LG, TR and PR phases, respectively.

Fig 4

Hierarchical cluster constructed with WGCNA at LG (A), TR (B), and PR (C) phases. Each vertical line (leaf) represents the corresponding genes.

Fig 5

Visual representation of the changes in the module structure between LG (A), TR (B), and PR (C) phases. Modules are illustrated with different colors.

Fig 6

PPI networks of co-expressed meta genes in brown module at LG (A), TR (B), and PR (C) phases. Changes in intra-module connectivity are highlighted at different phases.