Molecular approaches to enhance astaxanthin biosynthesis; future outlook: engineering of transcription factors in Haematococcus pluvialis

Microalgae are the preferred species for producing astaxanthin because they pose a low toxicity risk than chemical synthesis. Astaxanthin has multiple health benefits and is being used in: medicines, nutraceuticals, cosmetics, and functional foods. Haematococcus pluvialis is a model microalga for astaxanthin biosynthesis; however, its natural astaxanthin content is low. Therefore, it is necessary to develop methods to improve the biosynthesis of astaxanthin to meet industrial demands, making its commercialization cost-effective. Several strategies related to cultivation conditions are employed to enhance the biosynthesis of astaxanthin in H. pluvialis. However, the mechanism of its regulation by transcription factors is unknown. For the first time, this study critically reviewed the studies on identifying transcription factors, progress in H. pluvialis genetic transformation, and use of phytohormones that increase the gene expression related to astaxanthin biosynthesis. In addition, we propose future approaches, including (i) Cloning and characterization of transcription factors, (ii) Transcriptional engineering through overexpression of positive regulators or downregulation/silencing of negative regulators, (iii) Gene editing for enrichment or deletion of transcription factors binding sites, (iv) Hormonal modulation of transcription factors. This review provides considerable knowledge about the molecular regulation of astaxanthin biosynthesis and the existing research gap. Besides, it provides the basis for transcription factors mediated metabolic engineering of astaxanthin biosynthesis in H. pluvialis.

Automated summary

Microalgae, especially Haematococcus pluvialis, are preferred for the production of astaxanthin due to their low toxicity risk compared to chemical synthesis. This critical review discusses the strategies employed to enhance astaxanthin biosynthesis, including cultivation conditions and transcriptional regulation by factors that are yet to be identified. The review also proposes future approaches such as cloning and overexpression of positive regulators, gene editing, and hormonal modulation of transcription factors for efficient astaxanthin production. Overall, this study provides significant insights into the regulation and improvement of astaxanthin biosynthesis in H. pluvialis.