Production and excretion of astaxanthin by engineered Yarrowia lipolytica using plant oil as both the carbon source and the biocompatible extractant

Li, Ningyang; Han, Zhenlin; O’Donnell, Timothy J.; Kurasaki, Ryan; Kajihara, Lexie; Williams, Philip G.; Tang, Yinjie J.; Su, Wei

doi:10.1007/s00253-020-10753-2

Cited by 20 publications

(19 citation statements)

References 29 publications

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“…Retaining the leu2 gene in the genome can restore leucine biosynthesis, thus increasing the biomass. 45 To improve the biomass in the leucine auxotroph strain UHpDA*20, we attempted to restore its leucine biosynthesis. Restoration of leucine biosynthesis through the integration of leu2 into the genome of UHpDA*20 resulted in a five-fold increase in biomass in the new ULHpDA*20 strain when cultured in the medium CSM-Leu.…”

Section: Results Andsupporting

confidence: 75%

Production of High Levels of 3S,3′S-Astaxanthin in Yarrowia lipolytica via Iterative Metabolic Engineering

Zhu

Jiang

et al. 2022

J. Agric. Food Chem.

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Astaxanthin is a highly value-added keto-carotenoid compound. The astaxanthin 3S,3′S-isomer is more desirable for food additives, cosmetics, and pharmaceuticals due to health concerns about chemically synthesized counterparts with a mixture of three isomers. Biosynthesis of 3S,3′S-astaxanthin suffers from limited content and productivity. We engineered Yarrowia lipolytica to produce high levels of 3S,3′S-astaxanthin. We first assessed various β-carotene ketolases (CrtW) and β-carotene hydroxylases (CrtZ) from two algae and a plant. HpCrtW and HpCrtZ from Haematococcus pluvialis exhibited the strongest activity in converting β-carotene into astaxanthin in Y. lipolytica. We then fine-tuned the HpCrtW and HpCrtZ transcriptional expression by increasing the rounds of gene integration into the genome and applied a modular enzyme assembly of HpCrtW and HpCrtZ simultaneously. Next, we rescued leucine biosynthesis in the engineered Y. lipolytica, leading to a five-fold increase in biomass. The astaxanthin production achieved from these strategies was 3.3 g/L or 41.3 mg/g dry cell weight under fed-batch conditions, which is the highest level reported in microbial chassis to date. This study provides the potential for industrial production of 3S,3′S-astaxanthin, and this strategy empowers us to build a sustainable biorefinery platform for generating other value-added carotenoids in the future.

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Section: Results Andsupporting

confidence: 75%

Production of High Levels of 3S,3′S-Astaxanthin in Yarrowia lipolytica via Iterative Metabolic Engineering

Zhu

Jiang

et al. 2022

J. Agric. Food Chem.

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“…This oleaginous yeast has been successfully engineered for production of lycopene and β-carotene with significant high yields up to 21 mg/g DCW and 90 mg/g DCW, respectively [ [111] , [112] , [113] , [114] ]. Although, carotenoids biosynthesis in non-native microbes have achieved high yield in several hosts but the transformation from β-carotene to astaxanthin is still low [ 18 , 56 , [115] , [116] , [117] ]. The possible limitations might include enzymes expression levels and their substrates preferences, the accessibility of enzyme to substrates, precursors and cofactors supply, products and intermediates feedback inhibition, the interference with other biosynthetic pathways, and physiological stress due to the accumulation of astaxanthin or its intermediates.…”

Section: Strategies For Microbial Cell Factories Optimizationmentioning

confidence: 99%

“…However due to its hydrophobicity, the amount of secreted astaxanthin in the culture medium is very limited. Accordingly, the use of biocompatible organic solvents can facilitate the secretion of astaxanthin in the medium [ 115 ].…”

Section: Strategies For Microbial Cell Factories Optimizationmentioning

confidence: 99%

Optimization of microbial cell factories for astaxanthin production: Biosynthesis and regulations, engineering strategies and fermentation optimization strategies

Basiony

Ouyang

Wang

et al. 2022

Synthetic and Systems Biotechnology

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“…At last, considering that acetyl-CoA can be boosted in peroxisomes via the β-oxidation pathway when lipid stock was fed, 60 g/L glucose in YPDE medium was fully substituted with 33 g/L oleic acid (containing the same number of carbon atoms) for α-humulene production . It was found that the strain GQ2012 produced 693.2 ± 30.5 mg/L α-humulene in YPO33 medium, representing an 18.5% improvement compared to the titer in YPDE (Figure S4).…”

Section: Resultsmentioning

confidence: 99%

Harnessing Yarrowia lipolytica Peroxisomes as a Subcellular Factory for α-Humulene Overproduction

Guo

Shi

Peng

et al. 2021

J. Agric. Food Chem.

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The sesquiterpene α-humulene has been shown to have anti-inflammatory and anticancer activities, which has led to its vast application potential in medicine. However, α-humulene production methods including phytoextraction and chemical synthesis currently were limited to low yield, high costs, and expensive catalysts, which cannot meet the increasing market demand. In this study, Yarrowia lipolytica was developed as a robust cell factory for α-humulene production. The peroxisome in Y. lipolytica was first engineered to boost the synthesis of the sesquiterpene α-humulene. By compartmentalization of the α-humulene biosynthesis pathway, improving ATP and acetyl-CoA supply, and optimizing the gene copy numbers of rate-limiting enzymes, the engineered strain GQ2012 could produce 3.2 g/L α-humulene in a 5 L bioreactor, the highest α-humulene titer reported so far. Our study provides a valuable reference for highly sustainable production of terpenoids by peroxisome engineering in Y. lipolytica.

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Production and excretion of astaxanthin by engineered Yarrowia lipolytica using plant oil as both the carbon source and the biocompatible extractant

Cited by 20 publications

References 29 publications

Production of High Levels of 3S,3′S-Astaxanthin in Yarrowia lipolytica via Iterative Metabolic Engineering

Production of High Levels of 3S,3′S-Astaxanthin in Yarrowia lipolytica via Iterative Metabolic Engineering

Optimization of microbial cell factories for astaxanthin production: Biosynthesis and regulations, engineering strategies and fermentation optimization strategies

Harnessing Yarrowia lipolytica Peroxisomes as a Subcellular Factory for α-Humulene Overproduction

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