Cytochrome P450 Expression in Yarrowia lipolytica and Its Use in Steroid Biotransformation

Mauersberger, Stephan; Novikova, Ludmila A.; Shkumatov, V. M.

doi:10.1007/978-3-642-38583-4_7

Cited by 10 publications

(8 citation statements)

References 104 publications

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“…Notably, 93.2% pregnenolone was also observed to have remained inside the cell (Figure 5D), which is unlike its downstream derivatives such as progesterone that is continuously being pumped out of Y. lipolytica cells. 15 Promoter activities are reported to be affected by employing carbon sources, 23−25 and those controlled P450scc components were no exception (Figure S7). Therefore, it was speculated that the improvement on pregnenolone production under sunflower seed oil might also benefit from fine-tuning the expression levels of mCYP11A1, mAdx, and mAdR.…”

Section: ■ Results and Discussionmentioning

confidence: 98%

“…The recombinant Y. lipolytica presented in our previous study once achieved a highest campesterol titer of 453 mg/L in high density fermentation, 21 implying the great potential for downstream pregnenolone production. Mauersberger et al 15 also reported 8% conversion of 50 μM cholesterol by ethanolinduced expression of the human P450scc system in the recombinant diploid Y. lipolytica. Considering all above aspects, it is worth developing Y. lipolytica to be a promising platform for functional expression of P450scc to produce related pharmaceutical steroids.…”

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confidence: 94%

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Pregnenolone Overproduction in Yarrowia lipolytica by Integrative Components Pairing of the Cytochrome P450scc System

et al. 2019

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Microbial production of steroid drugs exhibits great potentials in much greener and more sustainable manners, in which engineering multiple cytochrome P450s is the prerequisite requirement. The pairing of multicomponents of P450 systems is a tremendous challenge. Herein, biosynthesis of pregnenolone (a common precursor of steroid drugs) in Yarrowia lipolytica was taken as a typical instance to explore the engineering strategy of the cytochrome P450 side-chain cleavage enzyme (P450scc) system. The mature forms of the components belonging to P450scc system, CYP11A1, adrenodoxin (Adx), and adrenodoxin reductase (AdR), were coexpressed in a former constructed campesterol producing strain. To maximize pregnenolone production, an integrative components pairing strategy was proposed for pairing the component sources and balancing the expression levels of CYP11A1, Adx, and AdR. Led by the above approaches, a 2344-fold improvement of pregnenolone titer was achieved at the shake flask level. Consequently, a highest reported pregnenolone titer of 78.0 mg/L in microbes was obtained in a 5 L bioreactor. Our study not only highlights the integrative components pairing of cytochrome P450scc as a general strategy for engineering other cytochrome P450s, but also provides a feasible and efficient platform of Y. lipolytica for other steroids production.

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Section: ■ Results and Discussionmentioning

confidence: 98%

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confidence: 94%

Pregnenolone Overproduction in Yarrowia lipolytica by Integrative Components Pairing of the Cytochrome P450scc System

et al. 2019

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“…Biotransformation of androstenedione (AD) to testosterone (TS) by S. cerevisiae was discovered as early as in 1937 [ 33 ], with the same function discovered in Schizosaccharomyces pombe later [ 34 ]. The biotransformation of steroid drugs by microbial strains was intensively studied in the 1990s, but limited to strain mining without comprehensive enzyme characterizations [ 32 , 35 ]. However, the wild-type strains are limited to specific types of reactions, which cannot be utilized to catalyze biotransformation beyond native catalytic capacity.…”

Section: Steroid Bioproduction In Yeast Through Biotransformationmentioning

confidence: 99%

Yeast as a promising heterologous host for steroid bioproduction

2020

Journal of Industrial Microbiology and Biotechnology

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With the rapid development of synthetic biology and metabolic engineering technologies, yeast has been generally considered as promising hosts for the bioproduction of secondary metabolites. Sterols are essential components of cell membrane, and are the precursors for the biosynthesis of steroid hormones, signaling molecules, and defense molecules in the higher eukaryotes, which are of pharmaceutical and agricultural significance. In this mini-review, we summarize the recent engineering efforts of using yeast to synthesize various steroids, and discuss the structural diversity that the current steroidproducing yeast can achieve, the challenge and the potential of using yeast as the bioproduction platform of various steroids from higher eukaryotes.

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“…This expression may aid in production of active steroids (Mauersberger et al, 2013) or other oxygenated FAs with antimicrobial properties.…”

Section: Production Of Fa-based Nutraceuticals and Pharmaceuticalsmentioning

confidence: 99%

Yarrowia lipolytica as an Oleaginous Cell Factory Platform for Production of Fatty Acid-Based Biofuel and Bioproducts

2014

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Today's biotechnologists seek new biocatalysts to meet the growing demand for the bioproducts. This review critically evaluates the potential use of Y. lipolytica as an oleaginous cell factory platform. This yeast has undergone extensive modifications for converting a wide range of hydrophobic and hydrophilic biomass, including alkane, oil, glycerol, and sugars to fatty acid-based products. This article highlights challenges in the development of this platform and provides an overview of strategies to enhance its potential in the sustainable production of biodiesel, functional dietary lipid compounds, and other value-added oleochemical compounds. Future applications of the recombinant Y. lipolytica platform are also discussed.

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Cytochrome P450 Expression in Yarrowia lipolytica and Its Use in Steroid Biotransformation

Cited by 10 publications

References 104 publications

Pregnenolone Overproduction in Yarrowia lipolytica by Integrative Components Pairing of the Cytochrome P450scc System

Pregnenolone Overproduction in Yarrowia lipolytica by Integrative Components Pairing of the Cytochrome P450scc System

Yeast as a promising heterologous host for steroid bioproduction

Yarrowia lipolytica as an Oleaginous Cell Factory Platform for Production of Fatty Acid-Based Biofuel and Bioproducts

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