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    Metabolic stressors stimulate the co-production of multiple high-value compounds accumulation in cyanobacterium Arthrospira

  • Farzaneh Fekrat,1,* Seyed Reza Jafariyan,2
    1. 1Agricultural Biotechnology Research Institute of Iran (ABRII), Education and Extension Organization (AREEO)
    2. Karaj Department of Education and Training (Area 2)


  • Introduction: Microalgal cultivation, as a green technology, has now received great attention. The biomass of cyanobacterium Arthrospira (i.e., Spirulina) studied as superfoods owing to contain about 50-70% protein, 15-25% carbohydrates, and 6-13% lipids, as well as substantial amounts of vitamins, minerals, and pigments (Phycocyanin, chlorophylls and carotenoids) which make the Arthrospira of excellent nutritional profiles and high-quality proteins (Salla et al. 2016; Fekrat et al. 2018). However, Arthrospira shows potential for being used as ingredients in the development of novel functional foods, which are among the top trends in the food industry (Lafarga et al. 2020). In the meantime, the suitable cultivation conditions for high-value compounds hyperaccumulation are the most challenging approach in Arthrospira platensis. However, to date, limited studies have been reported with respect to exploring various strategies for the co-production of multiple compounds in Arthrospira platensis. Arthrospira cells can simultaneously accumulate various valuable compounds; thus, the co-production of multiple products is achievable.
  • Methods: For the co-production of multiple metabolites in marine microalgae, numerous cultivation strategies have been using based on environmental conditions (Temperature, Salinity, Light), nutrient conditions (Nutrient sufficient/Deficient strategy, Semi-continuous/ Fed-batch strategy) and multiple factors integrated strategies (Two-stage cultivation with a combination of different Parameter) can be explored to enhance the co-production of multiple compounds (Ma et al. 2020).
  • Results: Arthrospira, with a flexible tricarboxylic acid (TCA) cycle, is an appropriate candidate for co-production of valuable metabolites by using metabolic stressors. The biosynthesis of lipids, pigments, carbohydrates, and proteins, is highly interconnected in the metabolic network and controlled by limiting steps. Metabolic flux may shift to different metabolites under specific cultivation conditions. Exploring novel cultivation strategies by integrating environmental and/or nutrient factors can be an effective way to improve the co-production of multiple compounds. Metabolic stress is a promising approach for metabolic pathway manipulation and elevation of interest metabolites production and cell growth. The TCA cycle is unusual and incomplete in cyanobacteria due to missing the 2-oxoglutarate dehydrogenase (OGDH) enzymes, and several shunts are identifiable. The GABA shunt is a variant of the TCA cycle that utilizes glutamate decarboxylase to convert glutamate to GABA. Then, GABA aminotransferase (GABA-T) converts GABA to alanine, and alanine aminotransferase (AlaAT) converts alanine to pyruvate and vice versa (Steinhauser et al. 2012). These findings revealed that GABA is one of the main components providing carbon for the TCA cycle and increasing lipid production in microalgae under abiotic stress conditions (Zhao et al. 2020). Hence, it seems that the level of pyruvate can be affected by the GABA shunt pathway. Further, an increase in GABA and alanine levels in the GABA shunt pathway probably can affect fatty acids and other metabolites induced. The aspartate transaminase reactions are the other critical variant pathways in cyanobacteria (the AspAT shunt), which permit the recycling of metabolites (Steinhauser et al. 2012). Aspartate aminotransferase is considered a critical enzyme for biomass production catalyzing the reversible reaction of 2-oxoglutarate, glutamate, aspartate, and oxaloacetic acid produced by the TCA cycle, linking nitrogen assimilation with carbon metabolism (Ghaffari et al. 2016). It also seems via the citrate-malate shunt that oxaloacetate is converted to pyruvate by oxaloacetate decarboxylase, which is a precursor to acetyl coenzyme A (Acetyl-CoA). Likewise, Acetyl-CoA. is a precursor for producing fatty acids and carotenoids. It has been evidenced that the classic TCA cycle produces energy agents (i.e., NADH & FADH) and biosynthetic precursors (for producing amino acids, lipids, and “heme” synthesis and linking to nitrogen metabolism), whereas the variants with their oxidative and reductive branches generate more biosynthetic precursors (Araújo et al. 2014).
  • Conclusion: Different patterns of desired metabolic profiles are easily attainable with some minor changes in growth conditions and/or medium compositions of cyanobacteria. More studies are needed to understand the key metabolic checkpoints and regulatory sites in primary intermediate metabolites utilized in Arthrospira. The presented strategy seems to provide an eco-friendly approach for reducing the production cost of biomass and valuable metabolites in A. platensis.
  • Keywords: Arthrospira platensis, Co-Production, metabolites, metabolic stress, TCA cycle