Metabolic engineering of cyanobacteria for the biosynthesis of lipid and carotenoid

Xi Wang

With the growing attentions to global warming, metabolic engineering of cyanobacteria for converting CO2 into valuable products has attracted great interests. In order to produce biofuels and natural products economically, enhancing the productivity of these metabolites becomes a critical need. In this work, metabolic engineering combined with metabolic flux modeling was conducted in the cyanobacterium Synechocystis sp. PCC 6803 for the photosynthetic production of lipid and astaxanthin. Lipid can serve as a precursor of fuels and astaxanthin is a natural co-product. As one of the emerging microbial cell factories, cyanobacteria have great metabolic potentials that are still largely unexplored. To achieve high-efficient conversion of CO2 into the targeted products, metabolic flux modeling was applied for the comprehensive analysis of metabolic pathways, including metabolic node (glycerol-3-phosphate), complex pathway (lipid biosynthesis), secondary metabolism (carotenoid biosynthesis), as well as identifying gene overexpression strategies (graphical user interface). First, enhanced glycerol-3-phosphate synthesis was engineered to increase lipid production in cyanobacteria. The mutant Synechocystis increased lipid content by 36%. The effects of glycerol-3-phosphate synthesis on cellular metabolism and lipid production were also investigated using flux modeling, and the results indicated that engineering glycerol-3-phosphate synthesis pathway was an important strategy for lipid production. Second, to explore the capability for producing high-value natural product, Synechocystis sp. PCC 6803 was metabolically engineered for astaxanthin production. By introducing the astaxanthin synthesis pathway and up-regulating the key genes at the upstream metabolic node of isoprenoid synthesis, the mutant was capable of producing astaxanthin, and the highest production yield obtained was up to 5.95 mg · L–1. Third, in silico pathway analysis was performed for lipid and carotenoid biosynthesis by using the constraint model of Synechocystis. Since up-regulation of key pathways is a basic strategy for overproducing target products, quantitative evaluation of metabolic pathway is critical to establish the standardized method for identifying up-regulated pathways. Lastly, to advance the modeling tool for determining gene overexpression strategies, a graphical user interface was developed for rapid identifying gene targets for targeted overproduction. This study provided experimental and modeling basis for metabolic engineering of cyanobacteria to efficiently convert CO2 into valuable products.

Metabolic engineering of cyanobacteria for the biosynthesis of lipid and carotenoid

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