Stepwise engineering of<i>Saccharomyces cerevisiae</i>to produce (+)-valencene and its related sesquiterpenes

Ouyang, Xiaodan; Cha, Yaping; Li, Wen; Zhu, Chaoyi; Zhu, Muzi; Li, Shuang; Zhuo, Min; Huang, Shaobin; Li, Jianjun

doi:10.1039/c9ra05558d

Cited by 26 publications

(29 citation statements)

References 47 publications

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“…These results were consistent with previous reports that the lower incubation temperature was beneficial for valencene accumulation. 68…”

Section: Resultsmentioning

confidence: 99%

“…These results were consistent with previous reports that the lower incubation temperature was beneficial for valencene accumulation. 68 To facilitate mannitol assimilation by yeast, the uptake rate and metabolic efficiency of mannitol need to be enhanced. As a result, the mannitol dehydrogenase coding gene DSF1 and mannitol transporter coding gene HXT13 under the control of the strong promoters P SED1L and P CDC19 were integrated into the genome of strain BN-913A.…”

Section: Characteristics Of Valencene Production By S Cerevisiae Duri...mentioning

confidence: 99%

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Efficient utilization of carbon to produce aromatic valencene in Saccharomyces cerevisiae using mannitol as the substrate

Zhu

You

et al. 2022

Green Chem.

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“…These results were consistent with previous reports that the lower incubation temperature was beneficial for valencene accumulation. 68…”

Section: Resultsmentioning

confidence: 99%

Section: Characteristics Of Valencene Production By S Cerevisiae Duri...mentioning

confidence: 99%

Efficient utilization of carbon to produce aromatic valencene in Saccharomyces cerevisiae using mannitol as the substrate

Zhu

You

et al. 2022

Green Chem.

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“…Different enzymes responsible for many microbial activities are also sensitive to high temperatures and are usually inactivated in this harsh condition [ 103 ]. Moreover, the role of temperature in (+)-valencene accumulation was investigated and found that remarkable enhancement in (+)-valencene concentration at 25 °C (87.2 mg/L) was observed compared to at 30 °C (20.6 mg/L) [ 21 ]. The benefit of lowering the temperature in the production of other relevant pharmaceuticals in yeast has also been previously reported in the case of plant lectins expression in Pichia pastoris [ 104 , 105 ].…”

Section: Factors Affecting Fermentation Process Of Pharmaceutical Terpenoidsmentioning

confidence: 99%

“…In the same line, S. cerevisiae has emerged as a model organism for the production of terpenoids since it has many additional advantages other than mentioned above, such as generally regarded as safe (GRAS) status, high genetic tractability, ease of manipulation, possessing universal endogenous MVA pathway, ability to express eukaryotic cytochrome P450 enzymes, robustness, relatively absence of secondary metabolites, high sugar catabolic, fast growth rate, and high tolerance against harsh industrial conditions [ 7 , 19 , 20 , 21 , 22 ].…”

Section: Introductionmentioning

confidence: 99%

Fermentation Strategies for Production of Pharmaceutical Terpenoids in Engineered Yeast

2021

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Terpenoids, also known as isoprenoids, are a broad and diverse class of plant natural products with significant industrial and pharmaceutical importance. Many of these natural products have antitumor, anti-inflammatory, antibacterial, antiviral, and antimalarial effects, support transdermal absorption, prevent and treat cardiovascular diseases, and have hypoglycemic activities. Production of these compounds are generally carried out through extraction from their natural sources or chemical synthesis. However, these processes are generally unsustainable, produce low yield, and result in wasting of substantial resources, most of them limited. Microbial production of terpenoids provides a sustainable and environment-friendly alternative. In recent years, the yeast Saccharomyces cerevisiae has become a suitable cell factory for industrial terpenoid biosynthesis due to developments in omics studies (genomics, transcriptomics, metabolomics, proteomics), and mathematical modeling. Besides that, fermentation development has a significant importance on achieving high titer, yield, and productivity (TYP) of these compounds. Up to now, there have been many studies and reviews reporting metabolic strategies for terpene biosynthesis. However, fermentation strategies have not been yet comprehensively discussed in the literature. This review summarizes recent studies of recombinant production of pharmaceutically important terpenoids by engineered yeast, S. cerevisiae, with special focus on fermentation strategies to increase TYP in order to meet industrial demands to feed the pharmaceutical market. Factors affecting recombinant terpenoids production are reviewed (strain design and fermentation parameters) and types of fermentation process (batch, fed-batch, and continuous) are discussed.

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“…Related research has used S. cerevisiae as the host strain to reconstruct its metabolic pathway in vivo and biosynthesize (+)-valencene and its derivatives (+)-nootkatone. Finally, the synthesis of (+)-nootkatone reached 53.7 mg/l through resting cell transformation (Ouyang et al, 2019 ). Recently, a biosynthetic pathway was constructed in S. cerevisiae to produce the (+)-nootkatone by overexpressing the CnVS, HPO, and ZSD1 combined with the MVA pathway engineering.…”

Section: Synthesis Of (+)-Nootkatone By Heterologous Synthesismentioning

confidence: 99%

Advances on (+)-nootkatone microbial biosynthesis and its related enzymes

Xiao

Ren

Fan

et al. 2021

Journal of Industrial Microbiology and Biotechnology

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(+)-Nootkatone is an important functional sesquiterpene and is comprehensively used in pharmaceutical, cosmetic, agricultural and food flavor industries. However, (+)-nootkatone is accumulated trace amounts in plants, and the demand for industry is mainly met by chemical methods which is harmful to the environment. The oxygen-containing sesquiterpenes prepared using microbial methods can be considered as ‘natural’. Microbial transformation has the advantages of mild reaction conditions, high efficiency, environmental protection and strong stereoselectivity, and has become an important method for the production of natural spices. The microbial biosynthesis of (+)-nootkatone from the main precursor (+)-valencene is summarized in this paper. Whole-cell systems of fungi, bacteria, microalgae and plant cells have been employed. It was described that the enzymes involved in the microbial biosynthesis of (+)-nootkatone, including cytochrome p450 enzymes, laccase, lipoxygenase and so on. More recently, the related enzymes were expressed in microbial hosts to heterologous produce (+)-nootkatone, such as Escherichia coli, Pichia pastoris, Yarrowia lipolytica and Saccharomyces cerevisiae. Finally, the development direction of research for realizing industrialization of microbial transformation was summarized and it provided many options for future improved bioprocesses.

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Stepwise engineering ofSaccharomyces cerevisiaeto produce (+)-valencene and its related sesquiterpenes

Abstract: A new yeast-based platform for the biosynthesis of (+)-valencene and its related sesquiterpenes found in grapefruit.

Cited by 26 publications

References 47 publications

Efficient utilization of carbon to produce aromatic valencene in Saccharomyces cerevisiae using mannitol as the substrate

Efficient utilization of carbon to produce aromatic valencene in Saccharomyces cerevisiae using mannitol as the substrate

Fermentation Strategies for Production of Pharmaceutical Terpenoids in Engineered Yeast

Advances on (+)-nootkatone microbial biosynthesis and its related enzymes

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