Johan Thevelein
Nutrient Sensing and Signaling in Yeast
Biotechnological applications of yeast
VIB Department of Molecular Microbiology, K.U.Leuven

PhD: Univ. of Leuven, Leuven, Belgium, '81 Postdoc: Yale University, Connecticut, USA, '82-'83 Scientific Director, Dept. of Molecular Microbiology since 2002

e-mail phone +32 16 32 15 00 ADDRESS

Current team members
Group leader: Johan Thevelein
Staff scientists: Beatriz Bonini Monge, Elke Nevoigt, Françoise Dumortier, Peter Verhaert
Expert: Bengt Persson
Postdoctoral scientists: Dries Castermans, Griet Van Zeebroeck, Maria Remedios Foulquié y Moreno, Marta Rubio-Texeira, Sofie Saerens, Tine Schaerlaekens, Yulia Popova, Yutaka Haitani
Ph.D. Students: Ben Souffriau, Frederik Paulussen, Georg Hubmann, Harish Kankipati, Johan Kriel, Jurgen Vandamme, Ken Peeters, Marlies Kimpe, Sarah Marinelli, Steven Haesendonckx, Stijn De Graeve, Tessa Moses, Thiago Martins Pais, Tom Den Abt, Wim Schepers, Yudi Yang
Support personnel: Catherina Coun, Eef Allegaert, Evy Vanderheyden, Kjell Lenaers, Mekonnen Demeke, Paul Vandecruys, Renata Wicik, Thomas Talpe, Timmy Reijnders, Tom Adriany

Keywords
transceptors stress tolerance - flavour ester synthesis - bioethanol production - medical applications

Science

Research in our group is focussed on two major topics: 1. the molecular genetics and biochemistry of nutrient-sensing and -signaling in yeast (Saccharomyces cerevisiae). and 2. the use of yeast for several biotechnological and medical applications

With respect to nutrient sensing and signaling, the main emphasis is on the control of the cAMP - protein kinase A pathway and the closely related fermentable-growth-medium (FGM) induced pathway by essential nutrients like glucose, nitrogen sources and phosphate. Glucose addition to glucose-deprived cells activates the cAMP pathway. Two sensing systems are involved in this
process: a G-protein coupled receptor (GPCR) system that acts in concert with a glucose-phosphorylation dependent system. The GPCR Gpr1 is a high-affinity sucrose and low-affinity glucose receptor. Residues located adjacent to the ligand-binding site have been identified using SCAM analysis. Recent work has shown that the Galpha protein Gpa2 does not interact with classical beta/gamma subunits and activates a bypass pathway of adenylate cyclase directly affecting PKA and composed of the kelch repeat proteins Krh1 and Krh2. Although addition of nitrogen sources or phosphate to nitrogen-starved or phosphate-starved cells, respectively, does not activate cAMP synthesis it affects the same protein kinase A targets as glucose addition to glucose-deprived cells. Typical rapid PKA-dependent effects are activation of trehalase, trehalose and glycogen mobilization, loss of stress resistance, repression of STRE/PDS-controlled genes and upshift of ribosomal protein gene expression. Amino acids are sensed by the general amino acid permease, Gap1, which thus functions both as a transporter and a receptor, or 'transceptor'. For ammonium and phosphate sensing, the transceptors Mep2 and Pho84, are involved respectively. SCAM analysis with
Gap1 and Pho84 has shown that the same amino acid or phosphate-binding site, respectively, is involved in transport and signaling. The yeast homologue of mammalian protein kinase B, Sch9, has been identified as a component of amino acid and ammonium but not of phosphate induced signaling.
The precise mechanisms involved in amino acid, ammonium and phosphate sensing and signaling for activation of PKA are a major focus of current research.

A second major focus in our group is the development of novel yeast strains for several industrial
applications: bioethanol production with 1st and 2nd generation substrates, beer brewing, wine and alcopops production, and baking. A novel genetic mapping technology has been developed which greatly facilitates the identification of genes involved in polygenic and quantitative properties, such as tolerance to different types of stress and flavour compound production. This will facilitate the development of improved industrial yeast strains. In addition, yeast is also used as a tool for the isolation and study of mammalian genes with medical interest, such as genes involved in Parkinson Disease, diabetes and glucose sensing in mammalian cells.

Press Release
See also press release (05/12/2008): Food can affect a cell in the same way hormones do based on a publication in Nature chemical biology (Van Zeebroeck et al., Nature chemical biology, 2008).

See also press release (01/08/2007): Plants and stress; key players on the thin line between life and death revealed based on a publication in Nature (Baena-González et al., Nature, 2007)

Van Zeebroeck G, Bonini B, Versele M, Thevelein J
Transport and signaling via the amino acid binding site of the yeast Gap1 amino acid transceptor
NAT CHEM BIOL 5, 45-52, 2009



Thevelein J, Voordeckers K
Functioning and evolutionary significance of nutrient transceptors
MOL BIOL EVOL 26, 2407-14, 2009



Peeters T, Louwet W, Gelade R, Nauwelaers D, Thevelein J, Versele M
Kelch-repeat proteins interacting with the Galpha protein Gpa2 bypass adenylate cyclase for direct regulation of protein kinase A in yeast
P NATL ACAD SCI USA 103, 13034-9, 2006



Van Nuland A, Vandormael P, Donaton M, Alenquer M, Lourenco A, Quintino E, Versele M, Thevelein J
Ammonium permease-based sensing mechanism for rapid ammonium activation of the protein kinase A pathway in yeast
MOL MICROBIOL 59, 1485-505, 2006



Kraakman L, Lemaire K, Ma P, Teunissen A, Donaton M, Van Dijck P, Winderickx J, De Winde J, Thevelein J
A Saccharomyces cerevisiae G-protein coupled receptor, Gpr1, is specifically required for glucose activation of the cAMP pathway during the transition to growth on glucose
MOL MICROBIOL 32, 1002-1012, 1999

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