Astaxanthin is a high-value red pigment and antioxidant widely used in the pharmaceutical, cosmetic, and food industries. However, the hydrophobicity of astaxanthin causes its low bioavailability. Glycosylation can substantially increase the water solubility of astaxanthin, thus enhancing its bioavailability, photostability, and biological activities. In this study, we report for the first time the heterologous production of glycosylated astaxanthin in Yarrowia lipolytica. By appropriate removal of the chloroplast transit peptide, carotenoid 4-hydroxy-β-ring 4-dehydrogenase (HBFD) and carotenoid β-ring 4-dehydrogenase (CBFD) from Adonis aestivalis were expressed in a β-carotene-producing Y. lipolytica strain, resulting in astaxanthin production with a yield of 0.59 mg/L, 0.05 mg/g DCW. This is the first time to successfully construct a plant-derived astaxanthin synthesis pathway in yeast. Modularized assembly of CBFD and HBFD, replacement of the promoter upstream CBFD, increasing the precursor β-carotene supply, and regulating the expressions of CBFD and HBFD led to a 4.9-fold increase in astaxanthin production (3.46 mg/L). Finally, introduction of crtX from Pantoea ananatis ATCC 19321 into the astaxanthin-producing strain enabled glycosylated astaxanthin production, and the yield reached 1.47 mg/L, which is the highest yield of microbially produced glycosylated astaxanthin reported to date.
Metabolic engineering is widely utilized in the food and other fields and has the benefits of low-cost substrates, ecofriendly fermentation processes, and efficient substrate synthesis. Microbial synthesis by metabolic engineering requires maintaining the productive capacity of the microorganism. Moreover, economic reasons limit the use of inducers in the exogenous synthesis pathway. Most unicellular microorganisms can interact by emitting signaling molecules; this mechanism, known as quorum sensing (QS), is an autoinduced system of microorganisms. With the deepening research on QS systems of different microorganisms, its components are widely used to regulate the metabolic synthesis of microorganisms as a dynamic regulatory system. In this Review, we described the typical bacterial QS mechanisms. Then, we summarized various regulatory strategies for QS and their applications to metabolic engineering. Finally, we underlined the potential for QS modularity in future metabolic engineering and suggested stimulating research on fungal QS systems.
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