L-carnitine, a medically relevant, amino acid-derived molecule is a valuable target for biotechnological production. Researchers at the Institute for Wine Biotechnology, Stellenbosch University has recently provided the first report of a metabolically engineered carnitine producing strain of the industrial yeast, Saccharomyces cerevisiae, an organism that does not natively produce its own carnitine. This was achieved by cloning and reconstructing the Neurospora crassa L-carnitine biosynthesis pathway in the baker’s yeast to create an L-carnitine producing strain. The engineered yeast strains are able to catalyze the synthesis of L-carnitine from the pathway’s precursor, trimethyllysine, as well as from intermediates. Several native S. cerevisiae genes were identified that contribute to, or interfere with, the heterologous pathway. This includes (i) the threonine aldolase Gly1p which effectively catalyzed the second step of the pathway, fulfilling the role of a serine hydroxymethyltransferase, (ii) the arginine transporter Can1p which was identified as the yeast transporter for trimethyllysine, and (iii) the two serine hydroxymethyltransferases, Shm1p and Shm2p, which reduced the flux through the heterologous pathway. The work opens opportunities for using an engineered, L-carnitine producing S. cerevisiae strain in various industrial applications.
The Craig Venter Institute built a synthetic bacterial genome, and George Church, Farren Isaacs and colleagues have engineered the E. coli genome using an innovative platform called MAGE and genome synthesis methods. Now the focus is on the first eukaryote, the yeast Saccharomyces cerevisiae. This organism has 16 linear chromosomes and a relatively compact (~14Mb total; ~12 Mb nonredundant) and well-understood genome. The synthetic yeast genome can be used to answer a wide variety of profound questions about fundamental properties of chromosomes, genome organization, gene content, function of RNA splicing, the extent to which small RNAs play a role in yeast biology, the distinction between prokaryotes and eukaryotes, and questions relating to genome structure and evolution. The availability of a fully synthetic genome will allow direct testing of evolutionary questions not otherwise approachable. The eventual “synthetic yeast” being designed and refined could eventually play an important practical role. Yeasts, and S. cerevisiae in particular, are preeminent organisms for industrial fermentations, with a wide variety of practical uses including ethanol production from agricultural products and by-products.