Recent Progress in the Chemistry and Biochemistry of Rifamycins

ABSTRACF The availability of a large number of natural and semisynthetic rifamycins made it possible to derive a clear relationship between structural features and activity against the target enzyme, the bacterial DNA-directed RNA polymerase (DDRP). Recent data are reported on the conformation of the active molecule in solution and on the Hansch approach for quantitative correlation between the in vitro antibacterial activity of several rifamycins and their lipophilicity. Some semisynthetic rifamycins were found to have a limited activity on the DDRP of rifampicin-resistant bacteria and of cytoplasmic DNA-viruses and on the RNA-directed DNA polymerase (RDDP) of oncogenic RNA viruses, but up-to-now there is no clear indication of the essential structural requisites for these activities. The biosynthetic pathways leading from acetate to propionate units to the ansamycins (rifamycins, tolipomycins, streptovaricins) are reviewed. The suggestion is made that utilization of different producing strains, their mutants, mixed fermentations and other techniques could yield a large number of new natural ansamycins to be tested on a battery of polymerizing enzymes (DDRP and RDDP).