Yeast enzymes bioengineering to generate bioactive compounds
Dr. María Fernández Lobato. Catedrática. Departamento de Biología Molecular. UAM.
Dr. Miguel Remacha Moreno. Catedrático. Departamento de Biología Molecular. UAM.
We work with microorganisms of biotechnological interest, mainly fungi and yeasts, producers of bioactive compounds. We try to connect the generation of knowledge to the development of biotechnological applications. Basically we focus on the characterization of new enzymes producing bioactive compounds, the analysis of their structural-functional determinants, the operational improvement using molecular biology tools and in obtaining and characterization of new molecules with potential industrial utility. We have patented in different countries the industrial applicability of most proteins characterized and designed methods for their attachment to solid supports.
During the last years we have been characterizing and studying several fungi and non-conventional yeast proteins (from genera Xanthophyllomyces, Schwanniomyces, Rhodotorula, etc.) showing glycosyltransferase activity, and applicable in the production of sugars with prebiotic properties. All are glycosylhydrolases (GH) structurally included in family GH32, 31, 13 or 18. Indeed, we have resolved the 3-D structure of the first yeast protein including in family GH32, assigned a function to the beta-sandwich domain that is present in all members of this family and proved that the oligomerization is directly involved in the substrate recognition and specificity. We have obtained numerous enzymatic variants that increase or alter the biosynthetic product patterns. Recently we have found that some of the characterized enzymes can glycosylate compounds with aromatic rings such as the hydroxytyrosol or pterostilbene (both antioxidants), which confers them a special biotechnological interest. We intend to extend our study to hydrolases including in other structural families, to increase and modify the transferase/biosynthetic activity of the enzymes studied, to scale up to industrial level the enzyme production and the products generated, as well as to validate the biological activity or give new uses to the molecules obtained. Objectives included in those of the consortia Glicoenz, Fish4Fish and a project founded by the Fundación Ramon Areces (XIX Concurso Nacional-Ciencias de la Vida y la Materia).