Sulfonamide resistance is often viewed as a consequence of antibiotic misuse; however, growing evidence reveals its widespread distribution across humans, animals, and the environment. Escherichia coli exhibits sulfamethoxazole resistance of 44–57%, with 93% of isolates carrying sul1 or sul2, while sul4 has recently emerged in companion animals; many resistant strains harbor...
Aminoacyl-tRNAs, charged by aminoacyl-tRNA synthetases with cognate amino acids, are essential for protein synthesis in primary metabolism. Beyond this canonical role, increasing evidence highlights their involvement in natural product biosynthesis. In this review, we first describe the biosynthesis of the aminoacyl nucleoside sulfamate ascamycin from Streptomyces sp. 80H647...
A defining characteristic of the Antibiotic Resistance crisis is the lack of substantial investment by the biopharmaceutical industry, which sees limited profit potential in novel antibiotics. We argue for redefining the salient problem for novel antibiotic development as the high rates of empiric treatment failure versus focusing only on infection deaths caused by a few specific...
Lincomycin A and celesticetin are representative members of the lincosamide class of clinically used antibiotics produced by Streptomyces species. Their distinctive chemical architectures arise from atypical biosynthetic gene clusters that lack well observed signature genes, and since the complete determination of the lincomycin A biosynthetic pathway, current research has...
Sporogen-AO1, a sporulation-promoting substance of Aspergillus oryzae was found to be a nonspecific translation inhibitor during screening of 22400 compounds. Sporogen-AO1 inhibited protein synthesis in cell-free protein synthesis (CFPS) systems derived from HeLa cell, wheat germ and yeast extracts, but not from E. coli S30 extracts. Sporogen-AO1 inhibited translation initiated...
Chemical and biological stimulus screening in a hypogean actinomycete was used to elicit secondary metabolism. Optimal biosynthesis of bioactive natural products was identified using Multiplexed Activity Profiling for determining dose-dependent activity via six single-cell biological readouts. Bioactive extracts were fractioned to establish candidate compounds for isolation using...
Global concerns about drug-resistant bacteria have underscored the need for new antimicrobial drugs. Emerging strategies in drug discovery include considering the third factors that influence drug activity. These factors include host-derived elements, adjuvants, and drug combinations, which are crucial in regulating antimicrobial efficacy. Traditional in vivo assessments have...
Mycobacterium tuberculosis is a bacterial pathogen, responsible for approximately 1.3 million deaths in 2022 through tuberculosis infections. The complex treatment regimen required to treat tuberculosis and growing rates of drug resistance, necessitates the development of new anti-mycobacterial agents. One approach is to repurpose drugs from other clinical applications...
The structure and conformation of antibiotic chryscandin, a structural analog of the terminus 3′-aminoacyladenylate moiety of tRNA, has been determined. The crystals belong to orthorhombic space group P212121. The structure was refined to an R value of 0.065 for 1872 reflections. The structure and conformation has been compared with that of puromycin. The sugar pucker is...
The deposited strain of the hazimicin producer, Micromonospora echinospora ssp. challisensis NRRL 12255 has considerable biosynthetic capabilities as revealed by genome scanning. Among these is a locus containing both type I and type II PKS genes. The presumed products of this locus, TLN-05220 (1) and TLN-05223 (2), bear a core backbone composed of six fused rings starting with a...
Cefiderocol, a novel siderophore cephalosporin, demonstrates promising in vitro activity against multidrug-resistant Gram-negative bacteria, including carbapenemase-producing strains. Nonetheless, only a few reports are available regarding the acquisition of resistance in clinical settings, primarily due to its recent usage. This study aimed to investigate cefiderocol resistance...
Waldiomycin is an inhibitor of histidine kinases (HKs). Although most HK inhibitors target the ATP-binding region, waldiomycin binds to the intracellular dimerization domain (DHp domain) with its naphthoquinone moiety presumed to interact with the conserved H-box region. To further develop inhibitors targeting the H-box, various 2-aminonaphthoquinones with cyclic, aliphatic, or...
Macrolactam antibiotics incorporating β-amino acid polyketide starter units, isolated primarily from Actinomycetes species, show significant biological activities. This review provides a detailed analysis into the biosynthetic studies of vicenistatin, a macrolactam antibiotic with a 3-aminoisobutyrate starter unit, as well as biosynthetic research on related macrolactam compounds...
The emergence of bacterial resistance to antibiotics poses a global health threat, necessitating innovative solutions. The contemporary challenge lies in bacterial resistance, impacting morbidity, mortality, and global economies. Antimicrobial peptides (AMPs) offer a promising avenue for addressing antibiotic resistance. The Antimicrobial Peptide Database catalogs 3569 peptides...
Spectinomycin is an aminocyclitol antibiotic with a unique ribosomal binding site. Prior synthetic modifications of spectinomycin have enhanced potency and antibacterial spectrum through addition at the 6’-position to produce trospectomycin and to the 3’-position to produce spectinamides and aminomethyl spectinomycins. This study focused on the design, synthesis, and evaluation...
A complete and detailed characterization of Rapamycin (1) and Prolylrapamycin (2) has been conducted by homo- and hetero-nuclear NMR experiments in DMSO-d6 along with HRMS and FT-IR spectra and DSCs analyses. The NMR experiments allowed the assignment of every single proton and carbon atom belonging to the two structures and the definitive confirm of the presence of a pyrrolidine...