Revolution of vitamin E production by starting from microbial fermented farnesene to isophytol

Ye, Ziling; Shu, Bin; Huang, Yanglei; Ma, Tian; Xiang, Zilei; Hu, Ben; Kuang, Zhaolin; Huang, Man; Lin, Xiaoying; Zhu, Tian; Deng, Zixin; Shen, Kun; Liu, Tiangang

doi:10.1016/j.xinn.2022.100228

Cited by 25 publications

(27 citation statements)

References 49 publications

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“…With the growing market demand, sustainable production methods of vitamin E are the need of the hour. Challenges in chemical synthesis have been overcome by successfully producing precursor molecules, such as isophytol, through fermentation of genetically engineered Saccharomyces cerevisiae and using them to synthesize vitamin E and reach an annual output of 30 000 tonnes . However, because of the nature of synthesis, racemic mixture of α-tocopherol is produced.…”

Section: Strategies For Multifold Enhancement Of Vitamin E Content In...mentioning

confidence: 99%

Antioxidant Green Factories: Toward Sustainable Production of Vitamin E in PlantIn VitroCultures

2023

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Vitamin E is a dietary supplement synthesized only by photosynthetic organisms and, hence, is an essential vitamin for human well-being. Because of the ever-increasing demand for natural vitamin E and limitations in existing synthesis modes, attempts to improve its yield using plant in vitro cultures have gained traction in recent years. With inflating industrial production costs, integrative approaches to conventional bioprocess optimization is the need of the hour for multifold vitamin E productivity enhancement. In this review, we briefly discuss the structure, isomers, and important metabolic routes of biosynthesis for vitamin E in plants. We then emphasize its vital role in human health and its industrial applications and highlight the market demand and supply. We illustrate the advantages of in vitro plant cell/tissue culture cultivation as an alternative to current commercial production platforms for natural vitamin E. We touch upon the conventional vitamin E metabolic pathway engineering strategies, such as single/ multigene overexpression and chloroplast engineering. We highlight the recent progress in plant systems biology to rationally identify metabolic bottlenecks and knockout targets in the vitamin E biosynthetic pathway. We then discuss bioprocess optimization strategies for sustainable vitamin E production, including media/process optimization, precursor/elicitor addition, and scale-up to bioreactors. We culminate the review with a short discussion on kinetic modeling to predict vitamin E production in plant cell cultures and suggestions on sustainable green extraction methods of vitamin E for reduced environmental impact. This review will be of interest to a wider research fraternity, including those from industry and academia working in the field of plant cell biology, plant biotechnology, and bioprocess engineering for phytochemical enhancement.

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Section: Strategies For Multifold Enhancement Of Vitamin E Content In...mentioning

confidence: 99%

Antioxidant Green Factories: Toward Sustainable Production of Vitamin E in PlantIn VitroCultures

2023

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“…Additionally, a route from farnesene to the C 18 ‐ketone by a Rh‐catalyzed C 3 ‐elongation reaction using β‐keto ester has been established on production scale (Scheme 9). Farnesene is obtained by microbial fermentation in yeast [180] . The process is based on the similar C 3 ‐elongation reaction of myrcene, which was developed in the 1980s.…”

Section: Industrial Synthesis Of Vitamin Ementioning

confidence: 99%

100 Years of Vitamin E: From Discovery to Commercialization

et al. 2022

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“…For example, α-farnesene works as a chemical signaling molecule to signal danger and to implicate the orientation of aphids and termites in nature [ 1 ]. Additionally, α-farnesene serves as an intermediate in the industry’s production of high-value products such as squalane, biofuel, vitamin E and vitamin K1 [ 2 , 3 , 4 ]. The use of α-farnesene in agriculture, chemicals, bioenergy, medicine and cosmetics is therefore significant economically [ 1 , 3 ].…”

Section: Introductionmentioning

confidence: 99%

“…The use of α-farnesene in agriculture, chemicals, bioenergy, medicine and cosmetics is therefore significant economically [ 1 , 3 ]. Plant extraction is the main way to make α-farnesene since it is widely present in plants, such as apples and Artemisia annua [ 1 , 4 , 5 ]. However, the drawbacks of plant extraction, such as poor yield, high production costs, the scarcity of feedstock and the severe environmental damage, restrict their industry use [ 3 , 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

“…However, the drawbacks of plant extraction, such as poor yield, high production costs, the scarcity of feedstock and the severe environmental damage, restrict their industry use [ 3 , 5 , 6 ]. Researchers focus on using microbial fermentation to produce α-farnesene as a result, and numerous efficient methods have been used to modify microorganisms to enhance the biosynthesis of α-farnesene, such as enhancing the α-farnesene biosynthesis pathway, blocking the downstream α-farnesene biosynthesis pathway, rewriting the central carbon metabolism, compartmentalizing the supply ways of precursors, relieving the inhibition of cell growth and optimizing the metabolic process [ 3 , 4 , 7 , 8 , 9 ]. In the previous study, we constructed an α-farnesene high-producing strain, Pichia pastoris X33-30, by the dual regulation of cytoplasm and peroxisomes [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

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Cofactor Engineering for Efficient Production of α-Farnesene by Rational Modification of NADPH and ATP Regeneration Pathway in Pichia pastoris

Chen

Liu

Zhang

et al. 2023

IJMS

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α-Farnesene, an acyclic volatile sesquiterpene, plays important roles in aircraft fuel, food flavoring, agriculture, pharmaceutical and chemical industries. Here, by re-creating the NADPH and ATP biosynthetic pathways in Pichia pastoris, we increased the production of α-farnesene. First, the native oxiPPP was recreated by overexpressing its essential enzymes or by inactivating glucose-6-phosphate isomerase (PGI). This revealed that the combined over-expression of ZWF1 and SOL3 increases α-farnesene production by improving NADPH supply, whereas inactivating PGI did not do so because it caused a reduction in cell growth. The next step was to introduce heterologous cPOS5 at various expression levels into P. pastoris. It was discovered that a low intensity expression of cPOS5 aided in the production of α-farnesene. Finally, ATP was increased by the overexpression of APRT and inactivation of GPD1. The resultant strain P. pastoris X33-38 produced 3.09 ± 0.37 g/L of α-farnesene in shake flask fermentation, which was 41.7% higher than that of the parent strain. These findings open a new avenue for the development of an industrial-strength α-farnesene producer by rationally modifying the NADPH and ATP regeneration pathways in P. pastoris.

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Revolution of vitamin E production by starting from microbial fermented farnesene to isophytol

Cited by 25 publications

References 49 publications

Antioxidant Green Factories: Toward Sustainable Production of Vitamin E in PlantIn VitroCultures

Antioxidant Green Factories: Toward Sustainable Production of Vitamin E in PlantIn VitroCultures

100 Years of Vitamin E: From Discovery to Commercialization

Cofactor Engineering for Efficient Production of α-Farnesene by Rational Modification of NADPH and ATP Regeneration Pathway in Pichia pastoris

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