Effectively Improve the Astaxanthin Production by Combined Additives Regulating Different Metabolic Nodes in Phaffia rhodozyma

Li, Zhipeng; Yang, Haoyi; Zheng, Chenhua; Du, Xiping; Ni, Hui; He, Ning; Yang, Liang; Li, You; Zhu, Yongqiang; Li, Lijun

doi:10.3389/fbioe.2021.812309

Cited by 5 publications

(6 citation statements)

References 44 publications

(72 reference statements)

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“…The glucose content in the medium decreased rapidly during the fermentation process, and the glucose content decreased from 20 g/L to 1.84 g/L at 96 h. Therefore, the carbohydrate carbon sources that could be taken up by cells were reduced, and the expression of the glycolytic pathway was downregulated. Moreover, astaxanthin production can be increased in the presence of reduced expression of the glycolytic pathway (Li et al, 2022).…”

Section: Corresponding Pathways Of Differential Metabolitesmentioning

confidence: 99%

“…These studies lack consideration of the original metabolic changes of P. rhodozyma without external forces. In addition, there are some studies focused on the metabolic changes of mutagenized P. rhodozyma (Li et al, 2022; Luna‐Flores et al, 2022; Luna‐Flores et al, 2023; Martinez‐Moya et al, 2011; Zhang et al, 2020). These studies have revealed the roles of various influencing factors in mutant P. rhodozyma , including various metabolic pathway branches and electron transport chains.…”

Section: Introductionmentioning

confidence: 99%

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Metabolomics of astaxanthin biosynthesis and corresponding regulation strategies in Phaffia rhodozyma

Yang

et al. 2023

Yeast

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Astaxanthin is a valuable carotenoid and is used as antioxidant and health care. Phaffia rhodozyma is a potential strain for the biosynthesis of astaxanthin. The unclear metabolic characteristics of P. rhodozyma at different metabolic stages hinder astaxanthin's promotion. This study is conducted to investigate metabolite changes based on quadrupole time‐of‐flight mass spectrometry metabolomics method. The results showed that the downregulation of purine, pyrimidine, amino acid synthesis, and glycolytic pathways contributed to astaxanthin biosynthesis. Meanwhile, the upregulation of lipid metabolites contributed to astaxanthin accumulation. Therefore, the regulation strategies were proposed based on this. The addition of sodium orthovanadate inhibited the amino acid pathway to increase astaxanthin concentration by 19.2%. And the addition of melatonin promoted lipid metabolism to increase the astaxanthin concentration by 30.3%. It further confirmed that inhibition of amino acid metabolism and promotion of lipid metabolism were beneficial for astaxanthin biosynthesis of P. rhodozyma. It is helpful in understanding metabolic pathways affecting astaxanthin of P. rhodozyma and provides regulatory strategies for metabolism.

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Section: Corresponding Pathways Of Differential Metabolitesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Metabolomics of astaxanthin biosynthesis and corresponding regulation strategies in Phaffia rhodozyma

Yang

et al. 2023

Yeast

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“…1 ). Pathway engineering strategies by overexpressing of the β-carotene ketolase or hydroxylase genes 18 , balancing their expression 19 , translational fusions or modularized complexes of carotenogenesis genes 20 – 22 as well as blocking of competing pathways have been shown to be effective for increasing astaxanthin production 23 . Moreover also bioprocess parameters such as temperature, pH 24 , light 25 and process optimization have been used to enhance astaxanthin production 26 , 27 .…”

Section: Introductionmentioning

confidence: 99%

Enhancing astaxanthin biosynthesis and pathway expansion towards glycosylated C40 carotenoids by Corynebacterium glutamicum

Göttl,

Meyer,

Schmitt

et al. 2024

Sci Rep

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Astaxanthin, a versatile C40 carotenoid prized for its applications in food, cosmetics, and health, is a bright red pigment with powerful antioxidant properties. To enhance astaxanthin production in Corynebacterium glutamicum, we employed rational pathway engineering strategies, focused on improving precursor availability and optimizing terminal oxy-functionalized C40 carotenoid biosynthesis. Our efforts resulted in an increased astaxanthin precursor supply with 1.5-fold higher β-carotene production with strain BETA6 (18 mg g−1 CDW). Further advancements in astaxanthin production were made by fine-tuning the expression of the β-carotene hydroxylase gene crtZ and β-carotene ketolase gene crtW, yielding a nearly fivefold increase in astaxanthin (strain ASTA**), with astaxanthin constituting 72% of total carotenoids. ASTA** was successfully transferred to a 2 L fed-batch fermentation with an enhanced titer of 103 mg L−1 astaxanthin with a volumetric productivity of 1.5 mg L−1 h−1. Based on this strain a pathway expansion was achieved towards glycosylated C40 carotenoids under heterologous expression of the glycosyltransferase gene crtX. To the best of our knowledge, this is the first time astaxanthin-β-d-diglucoside was produced with C. glutamicum achieving high titers of microbial C40 glucosides of 39 mg L−1. This study showcases the potential of pathway engineering to unlock novel C40 carotenoid variants for diverse industrial applications.

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“…Xanthophyllomyces dendrorhous ( Phaffia rhodozyma ) and Haematococcus pluvialis are the main natural producers of astaxanthin (Domínguez-Bocanegra et al 2007 ; Higuera-Ciapara et al 2006 ; Leu and Boussiba 2014 ; Li et al 2022 ; Mata-Gómez et al 2014 ; Torres-Haro et al 2021a ; Zhang et al 2020 ). Xanthophyllomyces dendrorhous is preferred for large-scale production since it synthesizes non-esterified astaxanthin as its main carotenoid (85% of total) at 20 °C and pH 6.0 (Kim et al 2005 ; Liu and Wu 2007 ; Ramírez et al 2001 ; Rodríguez-Sáiz et al 2010 ; Torres-Haro et al 2021b ; Wang et al 2019 ).…”

Section: Introductionmentioning

confidence: 99%

“…Xanthophyllomyces dendrorhous is preferred for large-scale production since it synthesizes non-esterified astaxanthin as its main carotenoid (85% of total) at 20 °C and pH 6.0 (Kim et al 2005 ; Liu and Wu 2007 ; Ramírez et al 2001 ; Rodríguez-Sáiz et al 2010 ; Torres-Haro et al 2021b ; Wang et al 2019 ). However, the astaxanthin production levels by wild type X. dendrorhous are low (170–200 µg astaxanthin/g of dry biomass) and uncompetitive compared to chemical synthesis (Andrewes et al 1976 ; Li et al 2022 ; Schmidt et al 2011 ; Torres-Haro et al 2021b ; Visser et al 2003 ).…”

Section: Introductionmentioning

confidence: 99%

Combined 6-benzylaminopurine and H2O2 stimulate the astaxanthin biosynthesis in Xanthophyllomyces dendrorhous

Torres-Haro,

Verdín,

Kirchmayr

et al. 2024

Appl Microbiol Biotechnol

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Astaxanthin is one of the most attractive carotenoids due to its high antioxidant activity and beneficial biological properties, while Xanthophyllomyces dendrorhous is one of its main microbial sources. Since astaxanthin is synthesized as a response to oxidative stress, several oxidative agents have been evaluated to increase X. dendrorhous astaxanthin yields. However, the extent of the stimulation is determined by the cellular damage caused by the applied oxidative agent. Phytohormones have also been reported as stimulants of astaxanthin biosynthesis acting directly on its metabolic pathway and indirectly promoting cellular resistance to reactive oxygen species. We reasoned that both oxidative agents and phytohormones lead to increased astaxanthin synthesis, but the latter could mitigate the drawbacks of the former. Thus, here, the stimulation on astaxanthin biosynthesis, as well as the cellular and transcriptional responses of wild type X. dendrorhous to phytohormones (6-benzylaminopurine, 6-BAP; abscisic acid, ABA; and indole-3-acetic acid, IAA), and oxidative agents (glutamate, menadione, H2O2, and/or Fe2+) were evaluated as a single or combined treatments. ABA and 6-BAP were the best individual stimulants leading to 2.24- and 2.60-fold astaxanthin biosynthesis increase, respectively. Nevertheless, the effect of combined 6-BAP and H2O2 led to a 3.69-fold astaxanthin synthesis increase (0.127 ± 0.018 mg astaxanthin/g biomass). Moreover, cell viability (> 82.75%) and mitochondrial activity (> 82.2%) remained almost intact in the combined treatment (6-BAP + H2O2) compared to control (< 52.17% cell viability; < 85.3% mitochondrial activity). On the other hand, mRNA levels of hmgR, idi, crtYB, crtR, and crtS, genes of the astaxanthin biosynthetic pathway, increased transiently along X. dendrorhous fermentation due to stimulations assayed in this study. Key points • Combined 6-BAP and H2O2 is the best treatment to increase astaxanthin yields in X. dendrorhous. • 6-BAP preserves cell integrity under oxidative H2O2 stress conditions. • 6-BAP and H2O2 increase transcriptional responses of hmgR, idi, and crt family genes transiently. Graphical abstract

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Effectively Improve the Astaxanthin Production by Combined Additives Regulating Different Metabolic Nodes in Phaffia rhodozyma

Cited by 5 publications

References 44 publications

Metabolomics of astaxanthin biosynthesis and corresponding regulation strategies in Phaffia rhodozyma

Metabolomics of astaxanthin biosynthesis and corresponding regulation strategies in Phaffia rhodozyma

Enhancing astaxanthin biosynthesis and pathway expansion towards glycosylated C40 carotenoids by Corynebacterium glutamicum

Combined 6-benzylaminopurine and H2O2 stimulate the astaxanthin biosynthesis in Xanthophyllomyces dendrorhous

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