IBR   13079
INSTITUTO DE BIOLOGIA MOLECULAR Y CELULAR DE ROSARIO
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
MUTATIONAL ANALYSIS OF ACYLTRANSFERASE PAPA5 IN ORDER TO MODIFY ITS ALCOHOL SPECIFICITY
Autor/es:
ROULET J.; BUSCHIAZZO A.; GRAMAJO H.; ARABOLAZA A.
Lugar:
Mar del Plata
Reunión:
Congreso; LI Reunión Anual Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2015
Resumen:
Wax esters are high-value neutral lipid compounds that serve a variety of functions in biological systems and have specific industrial uses as cosmetics, high-grade lubricants, and food additives. In our laboratory, we have developed a biosynthetic pathway that is based on an iterative PKS system in order to produce multi-methyl branched fatty acids (MBFA) and wax ester derivatives (MBE). This system consists of a PKS called mycocerosic acid synthase Mas, an acyl-AMP ligase Faal28, and an acyltransferase called PapA5 from Mycobacterium tuberculosis. The PapA5 protein can directly transfer the MBFA from Mas protein to alcohols. Structural analysis of PapA5 reveals a two-domain protein that shares unexpected similarity to structures of other unrelated acyltransferases. Binding pockets of PapA5 substrates were defined based on the modeling of the ligands of these homologous acyltransferases. It was shown that in vitro PapA5 can use a wide range of alcohols as substrate with more efficiency for medium chain and long chain alcohols, mainly 1-octanol. From the crystal structure of PapA5 we rationally designed and constructed mutants in residues predicted to have relevance in substrate specificity in order to improve short chain-alcohol affinity that finally generate more efficiently MBFA esters with different chemical structures and hence with different physicochemical properties