Production of lycopene by metabolically engineered <i>Pichia pastoris</i>

Zhang, Xinying; Wang, Denggang; Duan, Yehong; Zheng, Xueyun; Lin, Ying; Liang, Shuli

doi:10.1080/09168451.2019.1693250

Cited by 32 publications

(34 citation statements)

References 23 publications

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“…Recently, other yeasts such as K. phaffii , Kluyveromyces lactis , and Yarrowia lipolytica have emerged as advantageous cell factories. Among these, K. phaffii , commonly known as P. pastoris , has gained attention for marketing novel recombinant therapeutics ( Chen et al, 2020 ; Karbalaei et al, 2020 ; Spice et al, 2020 ; Zhang et al, 2020 ). To uncover and navigate the huge potential of P. pastoris in bioengineering, we need to establish straightforward strategies to assemble multi-component DNA constructs harboring genes and other essential regulatory elements.…”

Section: Discussionmentioning

confidence: 99%

Artificial Transcription Factors for Tuneable Gene Expression in Pichia pastoris

Naseri

Prause

Hamdo

2021

Front. Bioeng. Biotechnol.

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The non-conventional yeast Pichia pastoris (syn. Komagataella phaffii) has become a powerful eukaryotic expression platform for biopharmaceutical and biotechnological applications on both laboratory and industrial scales. Despite the fundamental role that artificial transcription factors (ATFs) play in the orthogonal control of gene expression in synthetic biology, a limited number of ATFs are available for P. pastoris. To establish orthogonal regulators for use in P. pastoris, we characterized ATFs derived from Arabidopsis TFs. The plant-derived ATFs contain the binding domain of TFs from the plant Arabidopsis thaliana, in combination with the activation domains of yeast GAL4 and plant EDLL and a synthetic promoter harboring the cognate cis-regulatory motifs. Chromosomally integrated ATFs and their binding sites (ATF/BSs) resulted in a wide spectrum of inducible transcriptional outputs in P. pastoris, ranging from as low as 1- to as high as ∼63-fold induction with only small growth defects. We demonstrated the application of ATF/BSs by generating P. pastoris cells that produce β-carotene. Notably, the productivity of β-carotene in P. pastoris was ∼4.8-fold higher than that in S. cerevisiae, reaching ∼59% of the β-carotene productivity obtained in a S. cerevisiae strain optimized for the production of the β–carotene precursor, farnesyl diphosphate, by rewiring the endogenous metabolic pathways using plant-derived ATF/BSs. Our data suggest that plant-derived regulators have a high degree of transferability from S. cerevisiae to P. pastoris. The plant-derived ATFs, together with their cognate binding sites, powerfully increase the repertoire of transcriptional regulatory modules for the tuning of protein expression levels required in metabolic engineering or synthetic biology in P. pastoris.

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Section: Discussionmentioning

confidence: 99%

Artificial Transcription Factors for Tuneable Gene Expression in Pichia pastoris

Naseri

Prause

Hamdo

2021

Front. Bioeng. Biotechnol.

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“…As a result, fed-batch production schemes have been designed to partition high cell density growth on glycerol/glucose and production on methanol. This strategy has successfully demonstrated the production of 714mg/L lycopene ( Zhang et al, 2020 ), (+)-ambrein, squalene ( Moser et al, 2018 ), and 208mg/L (+)-nootkatone ( Wriessnegger et al, 2014 ). Interestingly, the latter study successfully used an approach for CYP production that had failed in S. cerevisiae .…”

Section: Industrial Production From C1 Chemical Feedstocksmentioning

confidence: 99%

Diversifying Isoprenoid Platforms via Atypical Carbon Substrates and Non-model Microorganisms

Carruthers

Lee

2021

Front. Microbiol.

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Isoprenoid compounds are biologically ubiquitous, and their characteristic modularity has afforded products ranging from pharmaceuticals to biofuels. Isoprenoid production has been largely successful in Escherichia coli and Saccharomyces cerevisiae with metabolic engineering of the mevalonate (MVA) and methylerythritol phosphate (MEP) pathways coupled with the expression of heterologous terpene synthases. Yet conventional microbial chassis pose several major obstacles to successful commercialization including the affordability of sugar substrates at scale, precursor flux limitations, and intermediate feedback-inhibition. Now, recent studies have challenged typical isoprenoid paradigms by expanding the boundaries of terpene biosynthesis and using non-model organisms including those capable of metabolizing atypical C1 substrates. Conversely, investigations of non-model organisms have historically informed optimization in conventional microbes by tuning heterologous gene expression. Here, we review advances in isoprenoid biosynthesis with specific focus on the synergy between model and non-model organisms that may elevate the commercial viability of isoprenoid platforms by addressing the dichotomy between high titer production and inexpensive substrates.

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“… In a study published in 2020, a stepwise engineering approach was performed in P. pastoris to improve lycopene production, including the overexpression of the genes in the MVA pathway, overexpression of the gene GGPPS (encoding GGPP synthetase), and increasing the copy number of crt genes, and the obtained strain exhibited the highest lycopene production reported to date in P. pastoris, 9.319 mg/g of DCW and 714 mg/L …”

Section: Lycopene Production In Yeastmentioning

confidence: 99%

“…Another widely used yeast, P. pastoris, has been evaluated for carotenoid production, including xanthophylls, 105 β-carotene, and lycopene (Table 3). 16 In a study published in 2020, a stepwise engineering approach was performed in P. pastoris to improve lycopene production, including the overexpression of the genes in the MVA pathway, overexpression of the gene GGPPS (encoding GGPP synthetase), and increasing the copy number of crt genes, 106 and the obtained strain exhibited the highest lycopene production reported to date in P. pastoris, 9.319 mg/g of DCW and 714 mg/L. 106 P. pastoris is a highly successful system for heterologous protein expression, especially for vaccine production.…”

Section: Lipid Engineering and Membranementioning

confidence: 99%

Metabolic Engineering of Different Microbial Hosts for Lycopene Production

Xia

Zhang

et al. 2020

J. Agric. Food Chem.

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As a result of the extensive use of lycopene in a variety of fields, especially the dietary supplement and health food industries, the production of lycopene has attracted considerable interest. Lycopene can be obtained through extraction from vegetables and chemical synthesis. Alternatively, the microbial production of lycopene has been extensively researched in recent years. Various types of microbial hosts have been evaluated for their potential to accumulate a high level of lycopene. Metabolic engineering of the hosts and optimization of culture conditions are performed to enhance lycopene production. After years of research, great progress has been made in lycopene production. In this review, strategies used to improve lycopene production in different microbial hosts and the advantages and disadvantages of each microbial host are summarized. In addition, future perspectives of lycopene production in different microbial hosts are discussed.

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Production of lycopene by metabolically engineered Pichia pastoris

Cited by 32 publications

References 23 publications

Artificial Transcription Factors for Tuneable Gene Expression in Pichia pastoris

Artificial Transcription Factors for Tuneable Gene Expression in Pichia pastoris

Diversifying Isoprenoid Platforms via Atypical Carbon Substrates and Non-model Microorganisms

Metabolic Engineering of Different Microbial Hosts for Lycopene Production

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