Engineered Yeast Makes Steroids
Scientists have genetically reprogrammed yeast to produce a human steroid. This new method, described in the February 1998 issue of NatureBiotechnology, could be used for the industrial production of steroids. Steroids are natural substances that can be used, for example, to fight cancer and inflammation or as part of contraceptives. In addition, they cost less than products made by traditional chemical synthesis. The steroid progesterone helps maintain pregnancy: when taken by non-pregnant women, it tricks the body into preventing ovulation. Although the synthesis of progesterone-producing enzymes has been accomplished in vitro and in mammalian cell culture, these methods of manufacture are inefficient and expensive. Now, Denis Pompon and his colleagues at the CNRS Center for Molecular Genetics in Paris, in collaboration with Hoechst-Marion-Roussel and Transgene, have succeeded in reprogramming baker's yeast to produce progesterone and its precursor pregnenolone.
By inactivating a gene in yeast, the researchers stopped the production of a yeastoid called ergosterol. Instead, its precursor accumulates. In addition, they inserted a plant gene that produces an enzyme that converts these precursors into a cholesterol-like substance, a progesterone precursor. Three cow genes provided enzymes and cofactors that produce pregnenolone from the cholesterol-like substance. Finally, an enzyme encoded by a human gene converted pregnenolone into progesterone.
Within 4 days, the yeasty soup produced 60 to 100 mg of pregnenolone per liter and smaller amounts of progesterone."This achievement marks a milestone in the production of steroid hormones by microorganisms," said Michael Waterman, biochemist at Vanderbilt University Medical Center in Nashville, Tennessee. Going one step further, Pompon says, yield could be increased even more to meet "industrial demands for economic competition for chemical synthesis."