Producción CyT

BIOCELL 2009, vol 33 - Analysis of the final steps of megalomicin biosynthesis: Generation of new megalomicins analogues

Congreso

Autoría:

USEGLIO, MARIANA ; Salvador Peirú ; Eduardo Rodríguez ; Hugo Gramajo

Fecha:

2009

Editorial y Lugar de Edición:

Tech Science Press

Resumen *

Megalomicins are terapeutically important compounds which have antiparasitic, antiviral and antibacterial properties. They are produced by Micromonospora megalomicea and differ from erythromycin by the addition of a unique deoxyamino sugar, megosamine, to the C6 hydroxyl.In this work we identified the genes involved in the megalomycin pathway and validate it by the expression of the genes in Escherichia coli. LC/MS/MS analysis of the dTDP-sugar intermediates produce by operons containing diferent sets of genes showed that production of dTDP-L-megosamine from dTDP-4-keto-6-deoxy-D-glucose require only five biosynthetic steps, the first three step are common with others TDP-sugar pathways while the last two are specific from this pathway. The validation of this pathway was demonstrated by conversion of EryC to Megalomicina A.In addition, we feed different erythromycin C analogues, erythromicin A and azithromycin to generate new compounds, 6-megosaminil-erithromycin A and 6-megosaminil-azithromycin, respectly. These results indicate a significant flexibility of proteins which are MegDI-MegDVI, involved in the L-megosamine transference to alternative macrolactone. The antiparasitic and antibacterial activity of these new compounds is being evaluated. Información suministrada por el agente en SIGEVA