Self-sufficient biosynthesis of pregnenolone and progesterone in engineered yeast

@article{Duport1998SelfsufficientBO,
  title={Self-sufficient biosynthesis of pregnenolone and progesterone in engineered yeast},
  author={Catherine Duport and Roberto Spagnoli and Eric Degryse and Denis Pompon},
  journal={Nature Biotechnology},
  year={1998},
  volume={16},
  pages={186-189}
}
The first two steps of the steroidogenic pathway were reproduced in Saccharomyces cerevisiae. Engineering of sterol biosynthesis by disruption of the Δ22-desaturase gene and introduction of the Arabidopsis thaliana Δ7-reductase activity and coexpression of bovine side chain cleavage cytochrome P450, adrenodoxin, and adrenodoxin reductase, lead to pregnenolone biosynthesis from a simple carbon source. Following additional coexpression of human β-hydroxysteroid dehydrogenase/isomerase… 
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114 Citations

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KduD from E. coli is therefore a promiscuous enzyme that has a predicted role in sugar conversion in vivo but can be used for the production of valuable bioactive 20-hydroxysteroids.
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The findings indicate that genes encoding soluble proteins should be examined as candidates for actual steroid dehydrogenase activity in Schizosaccharomyces pombe, and more than one steroid dehydration homologue is likely to occur.
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It is shown that the distribution between pyruvate and glyceraldehyde 3‐phosphate (G3P) is a major factor that can limit isoprenoid production yields in E. coli, and modifications that achieve a more equitable distribution between the two precursors are able to increase the lycopene yield in metabolically engineered E. bacteria.
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