PubMed Health⌕ Search
Home/Archive/PubMed

PubMed · 1367143

Second-generation products: antibiotics.

J T Fayerman
View original source ↗Export metadata ↓

Abstract

There has been outstanding progress in gene cloning from microorganisms producing useful antibiotics. Especially noteworthy is the cloning of a gene for cephalosporin biosynthesis that, with increased copy number, helps to overcome a rate-limiting step in biosynthesis. Although this technology is often fraught with unexpected difficulties, not the least of which is gene expression, yield improvement is a practical application with clear financial benefits to the pharmaceutical industry. Although access to cloned genes for antibiotic biosynthesis is becoming common, expression of the cloned genes in a manner such that yield improvement is achieved is a challenge that will be exciting and beneficial in years to come. Heterologous (interspecies) gene expression in antibiotic-producing microorganisms, particularly the actinomycetes, must be successful if hybrid antibiotics are to be produced. Currently, there are no documented examples of heterologous gene cloning to yield a hybrid antibiotic of utility. Even though a hybrid antibiotic structure has been reported as a result of heterologous gene cloning, the antibiotic is not clinically useful, and the two species used in the experiments are closely related. Although technological advances have enabled successful gene cloning, insufficient attention has been given to the issue of gene expression, particularly heterologous gene expression. The need to develop heterologous gene expression systems is urgent. Until this is done, the inability to express cloned antibiotic biosynthesis genes in heterologous hosts could be a barrier to the generation of useful hybrid antibiotics. The potential for a wide array of new antibiotic compounds that could be generated by gene-cloning technology is vast. At least until the limitations of heterologous gene expression are overcome, the best available screening technology (including molecular and immunological screens) and chemistry might best serve as the most prolific means of discovering useful new antibiotics for agriculture and medicine.

Explore related subjects

Anti-Bacterial AgentsBiotechnologyLactamsMacrolidesJournal ArticleReview

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

J T Fayerman. 1991. Second-generation products: antibiotics.. https://pubmed.ncbi.nlm.nih.gov/1367143/

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2026

Total Synthesis and Structural Revision of Rhabdobranin Reveals a Cryptic Gram-Negative Antibiotic.

Gram-negative bacteria present a major clinical challenge but also remain an underexplored source of antibacterial natural products. Resistance-guided genome mining of the entomopathogenic symbiont Xenorhabdus identified the rdb biosynthetic gene cluster, which encodes a putative prodrug antibiotic, pre-rhabdobranin. However, the inability to isolate the proposed active metabolite, rhabdobranin, has prevented direct functional evaluation. Here we report a convergent total synthesis of the proposed structure of pre-rhabdobranin B, which revealed a stereochemical misassignment at the N-terminal arginine residue. Synthesis of both rhabdobranin epimers showed that, although they are nearly indistinguishable by standard analytical methods, inversion at this single stereocenter has a pronounced effect on antibacterial activity. Biological evaluation of the revised rhabdobranin structure revealed potent antibacterial activity against Gram-negative pathogens, including WHO critical-priority carbapenem-resistant Klebsiella pneumoniae. Cellular and biochemical profiling implicated inhibition of protein biosynthesis as its principal antibacterial mechanism. We further show that the GNAT-family acetyltransferase RdbK N-acetylates rhabdobranin, attenuating its activity and establishing a secondary self-resistance mechanism. These findings validate resistance-gene-guided discovery in Gram-negative symbionts as a strategy for uncovering cryptic antibiotics and identify rhabdobranin as a promising scaffold for Gram-negative antibiotic development.

Anti-Bacterial Agents↗
PubMed2026

Environmental antibiotic contamination and AMR: Integrating pathways, impacts, and artificial intelligence-driven mitigation.

The widespread contamination of the environment with antibiotic residues is a significant factor contributing to the global crisis of antimicrobial resistance (AMR). Antibiotics from various sources, such as effluents from municipal and hospital wastewater treatment plants, agricultural runoffs, discharges from pharmaceutical manufacturing and improper disposal of expired or unused medicines, create selective pressures in the spread of antibiotic resistance genes. These environmental reservoirs act as hotspots for horizontal gene transfer, facilitating the emergence of multidrug-resistant pathogens. Conventional detection methods including culture-based assays, chromatographic quantification, and molecular diagnostics, provide essential insights but are limited by low throughput, reduced sensitivity to new Antibiotic Resistance Genes, and challenges in real-time monitoring across complex environments. Recent advances, such as whole-genome sequencing, metagenomics, and biosensor-based detection, help to address these gaps by enabling more comprehensive surveillance of the resistome. Artificial intelligence further enhances these approaches by improving data interpretation and pattern recognition, thus complementing traditional and molecular methods rather than replacing them. This review examines the pathways of environmental antibiotic contamination, ecological and health impacts of AMR, and limitations of conventional detection methods. It aims to clarify how these pathways contribute to the AMR crisis, assess the effectiveness of existing surveillance techniques, and identify gaps in current research.

Anti-Bacterial Agents↗
PubMed2026

Discovery of Glycosylated β-Amino Acid-Containing Macrolactams from Nonomuraea sp. 0L2P via Genome Mining.

β-Amino acid-containing macrolactams (β-AACMs) are a class of bioactive natural products characterized by nitrogen-containing starter units within polyketide-derived macrocycles. Here, we report four previously undescribed macrolactams, gruelactams A-D (1-4), from Nonomuraea sp. 0L2P, discovered through an integrated approach combining genome mining, 15N-labeling, and antibacterial screening. Their planar structures were elucidated by comprehensive spectroscopic analyses, including 1D and 2D NMR and HRESI-MS, and their configurations were partially assigned based on ROESY data and bioinformatic analysis. Genome sequencing and antiSMASH analysis identified a putative type I polyketide synthase (PKS) biosynthetic gene cluster, enabling the proposal of a biosynthetic pathway. Bioactivity assays showed that gruelactam D (4) exhibits antibacterial activity against Bacillus cereus and Staphylococcus aureus, with MIC values of 8 and 16 μg/mL, respectively. These findings expand the chemical diversity of β-AACMs and demonstrate the utility of genome-guided approaches for discovering bioactive natural products from rare actinomycetes.

Anti-Bacterial Agents↗