Metabologenomic approach to discover aromatic polyketides, angucycline antimicrobial compounds produced by alkaliphilic Streptomyces.

Integrated chemical and genomic analysis of lipopeptides produced by Bacillus velezensis CMRP4489 with antifungal activity

The present study is the first to report the antifungal activity of bacillopeptins against Sclerotinia sclerotiorum, a fungus responsible for white mold.

Screening of Actinomycetes from Rhizosphere Soils for L-glutaminase Production

The integrated experimental and in silico approach highlights soil-derived actinomycetes as versatile and sustainable bioresources with significant pharmaceutical and biotechnological potential, emphasizing their role in combating antimicrobial resistance and enabling the rational development of novel therapeutic and industrial products.

Genomic and Metabolomic Profiling of Streptomyces anulatus 89: Molecular Phylogeny and Biosynthesis of Antitumor Antibiotics

The investigated crude extract exhibited pronounced antitumor activity, making it a promising candidate for further studies, and the underlying hypothesis suggested that strains with broad adaptive potential may serve as promising producers of natural products with antitumor properties.

Statistical optimization of extracellular antimicrobial metabolite production by Streptomyces enissocaesilis ASB isolate targeting multidrug-resistant pathogens

Capsimycin derivatives from Streptomyces sp. PH9007 as α‑glucosidase inhibitors and insights into their biosynthetic gene cluster

The increasing number of individuals with diabetes mellitus (DM) highlights the need to develop new diabetes medications. Polycyclic tetramate macrolactams (PTMs), characterized by a macrocyclic lactam containing an integrated tetramic acid ring, constitute an expanding group of extensively dispersed natural compounds with diverse biological functions. In this study, two Streptomyces strains were isolated from the roots of the medicinal plant Sinomenium acutum . Using the Global Natural Products Social (GNPS) web platform, three PTMs, namely, capsimycin (4), capsimycin B (5), and capsimycin G (6), were extracted from Streptomyces sp. PH9007, which was isolated from Sinomenium acutum . Compounds 4 and 5 inhibited α-glucosidase, with 4 and 5 exhibiting IC 50 values of 484.6 ± 14.10 μM and 366.9 ± 12.85 μM, respectively. Compound 5 also exhibited antibacterial and antifungal activities, with MICs of 16 µg/mL against MRSA, Staphylococcus aureus ATCC 29213 and Candida albicans CMCC 98001. The results of fluorescence quenching, UV–visible spectroscopy, molecular docking and molecular dynamics simulations of 5 with α-glucosidase indicated that this compound binds better with α-glucosidase. Whole-genome sequencing of PH9007 revealed a 6, 339, 217 bp chromosome and two plasmids (83, 532 bp and 167, 087 bp) containing 25 biosynthetic gene clusters (BGCs), including one exhibiting 56% sequence similarity to the ikarugamycin BGC. Furthermore, bioinformatics analysis revealed that the ikarugamycin BGC is widely distributed in microorganisms. Overall, this study highlights that PTM-type compounds may serve as promising compounds for the further development of α-glucosidase inhibitors and lays the foundation for research on their biosynthesis.

Genetic dissection of persiathiacin biosynthesis defines hierarchical P450 oxidations and reveals a more potent antitubercular intermediate

Thiopeptides are ribosomally synthesized and post-translationally modified peptides (RiPPs) that form complex bioactive scaffolds through extensive enzymatic tailoring. The polyglycosylated thiopeptides persiathiacins, exhibit potent activity against multidrug-resistant Mycobacterium tuberculosis (Mtb) and methicillin-resistant Staphylococcus aureus (MRSA). The persiathiacin biosynthetic gene cluster encodes six cytochrome P450 (CYP) enzymes, but the logic of their oxidative modifications was unknown. Here, we establish a protoplast-based genetic system for Actinokineospora and systematically assign functions to all P450s. We demonstrate that PerX hydroxylates the central thiazole, PerV installs the third indole–core crosslink required for macrocyclization, and PerT, not PerU, catalyses indole N-hydroxylation. Combined gene inactivation and metabolite profiling reveal a hierarchical enzymatic sequence leading to the mature scaffold prior to sugar installation. Notably, the intermediate accumulating in the ΩperX mutant exhibits enhanced anti-M. tuberculosis potency compared to persiathiacin A (IC50 = 0.07 vs 1.5 µg mL−1). These results define the enzymatic logic and temporal organization of persiathiacin biosynthesis, providing a conceptual framework for rational diversification of complex thiopeptide natural products.