Title : Potential of Yarrowia lipolytica as a microbial cell factory for sustainable anthocyanin bioproduction
Abstract:
The global agrifood system faces significant challenges related to both human and planetary health. Food additives are one tool utilized by the food industry to address the need for longer shelf-lives, reduce food waste and loss, increase the palatability of alternative protein options and improve nutritional profiles. Natural food additives are now the preference from both consumers and regulatory bodies. Anthocyanins, a class of water-soluble flavonoids present in most flowering plants, have received increasing attention due to their multiple bioactive properties imbuing them with the dual effect of both colorant and preservative. However, challenges associated with their method of production, currently unsustainable and expensive plant-extraction, have limited their adoption. This study aims to address this bottleneck by developing Yarrowia lipolytica microbial cell factories for anthocyanin production, specifically the red cyanidin-3-o- glucoside. The oleaginous yeast Y. lipolytica holds potential as a superior host than the currently explored Saccharomyces cerevisiae and Escherichia coli given not only its promising traits as an industrial workhorse, but subcellular structures ideal for expression of pathway proteins and high flux for the key precursor malonyl-CoA. Metabolic engineering and synthetic biology tools have been adopted to introduce codon- optimized enzymes from the plant pathway in Y. lipolytica. Different genomic backgrounds, expression levels and gene integration strategies have been evaluated to identify a high-producing strain of the key flavanone precursor naringenin, with titers of up to 357mg/L at the shake-flask level. For dihydroflavonol and anthocyanin pathway modules, where by-product formation has been a major challenge across microbial hosts, the design of a synthetic metabolon, inspired by the plant system’s spatial regulation of the pathway, is being explored. This is currently under work. Y. lipolytica’s ability to consume low-cost carbon substrates such as agricultural waste and by-products, holds promise for the inexpensive and sustainable production of anthocyanins as well as a diversity of plant specialized compounds.
