Biosynthesis
Despite the fact that Rifamycin B is a mild antibacterial compound, it is known to be the precursor of various other clinically-utilized potent derivatives. The general scheme of biosynthesis starts with the uncommon starting unit, 3-amino-5-dihydroxybenzoic acid (AHBA), via type I polyketide pathway (PKS I) in which chain extension is performed using 2 acetate and 8 propionate units. AHBA is believed to have originated from the Shikimate pathway, however this was not incorporated into the biosynthetic mechanism. This is due to the observation that 3 amino-acid analogues converted into AHBA in cell-free extracts of A. mediterranei.
The rif cluster is responsible for the biosynthesis of rifamycins. It contains genes rifG through rifN, which were shown to biosynthesize AHBA. RifK, rifL, rifM, and rifN are believed to act as transaminases in order to form the AHBA precursor kanosamine. "RifH" encodes aminoDAHP synthase that catalyzes the condensation between 1-deoxy-1-imino-d-erythrose 4-phosphate and phosphoenolpyruvate. RifA through rifE encode a type I polyketide synthase module, with the loading module being a non-ribosomal peptide synthase. In all, rifA-E assemble a linear undecaketide and are followed by rifF, which encodes an amide synthase and causes the undecaketide to release and form a macrolactam structure. Moreover, the rif cluster contains various regulatory proteins and glycosylating genes that appear to be silent. Other types of genes seem to perform post-synthase modifications of the original polyketide.
Read more about this topic: Rifamycin