Recent Biosynthetic Studies on Antibiotics

Abstract

During recent years our re-earch group ha. been engaged in biobynthetic studies dealing Tt-ith antibiotic, of two different sort>. In a continuing qtudy we have investigated the biosynthetic origin. of the very important aminocyclitol antibiotics, which include gentamicin. neomycin, streptomycin, -pectinoniycin, etc. This topic has been reriened extensively vithin the past \- ear (1. 2 . 3). E-AMINOACETOPHENONEFIG. 2. Blternative biosynthetic pathxays t o m-aminoacetophenone.

Deciphering Pactamycin Biosynthesis and Engineered Production of New Pactamycin Analogues

“…This functional group is lost during the formation of the 2-oxazolidone ring structure present in the pactamycate derivatives. [9,23] To further evaluate and compare the in vitro efficacy of de-6-MSA-pactamycin with that of pactamycin, dose-response experiments were done by using a broth microdilution method with 0.01 (or 0.1)-100 mm concentrations of pactamycin and de-6-MSA-pactamycin ( Figure 7). In all of the studies, de-6-MSA-pactamycin showed equivalent biological activity with the parent molecule, pactamycin; this suggests that the 6-MSA moiety is not essential for activity.…”

“…[7] Pactamycin (1) consists of a five-membered ring aminocyclitol unit, which is rich in stereogenic centers, two aromatic rings (6-methylsalicylic acid (6-MSA) and 3-aminoacetophenone) and a 1,1-dimethylurea. [8,9] This compound showed potent antibacterial activities against Gram-positive and Gramnegative bacteria, [3] as well as strong anti-tumor activity. [3] However, its development as an antibiotic or an anticancer drug was hampered by its high toxicity profile.…”

“…Until recently, the biosynthetic studies of pactamycin have only been performed by conventional feeding experiments with isotopically labeled precursors. [9,10] It has been suggested that the five-membered ring aminocyclitol moiety of pactamycin is derived from glucose, whereas the 6-MSA moiety is synthesized from acetic acid. The aminoacetophenone moiety is derived from an unknown branch of the amino-shikimate pathway.…”

Biosynthetic Studies on Antibiotics

“…These showed efficient incorporation of 2301 The five thiazole rings would be predicted to arise from a molecule of cysteine plus the carboxyl group of another acid or amino acid. This expectation is confirmed by the finding that ~,~-[3-'~C]cysteine labels C-5 in all the thiazole rings as well as C-3 in the cysteine moiety.…”

ChemInform Abstract: Biosynthetic Studies on Antibiotics

“…Since nosiheptide 78 is evidently a modified peptide, the incorporation of a variety of 14C-labeled amino acids was tested in a series of preliminary feeding experiments 2301 The five thiazole rings would be predicted to arise from a molecule of cysteine plus the carboxyl group of another acid or amino acid. This expectation is confirmed by the finding that ~,~-[3-'~C]cysteine labels C-5 in all the thiazole rings as well as C-3 in the cysteine moiety.…”