Biology subjects

Peschel, G.

Publications and source records attributed to Peschel, G..

3 recordsLinked to original sources

bioRxiv2026

Antimicrobial and Cytotoxic Lysolipins I-M Isolated from Streptomyces sp. P8-2B18

Lysolipin I (1) is a highly bioactive xanthone with strong antibacterial and cytotoxic properties. Given the limited number of lysolipin analogues, discovery of new natural lysolipin derivatives is important for understanding their structure-activity relationships. A soil-derived Streptomyces sp. P8-2B18 harbors a putative lysolipin biosynthetic gene cluster and LC-MS based metabolomic analysis revealed the production of lysolipin I along with unreported analogues. Large-scale fermentation followed by isolation led to the discovery of four new analogues, lysolipins J-M (2- 5), the structures of which were elucidated by mass spectrometric and NMR spectroscopic data analyses. Lysolipin L features a five-membered lactam F ring, which was unprecedented in reported lysolipins. Lysolipin M has a novel skeleton, with an extra methyl (Me-36) and a glycosyl group replacing a 1,3-oxane ring in lysolipin I. While lysolipins I, J and K displayed strong activity against Staphylococcus aureus and Aspergillus flavus with MIC values ranging from 0.25 to 4 g/mL and lysolipin L showed only moderate activities, lysolipin M was inactive (>50 g/mL). Lysolipins I-K showed potent cytotoxic activity against prostate cancer cell lines LNCaP and C4-2B, with IC50 values in the submicromolar range. In contrast, lysolipin L exhibited no cytotoxicity and lysolipin M exhibited substantially reduced potency. Their broad, non-selective bioactivities restricted their applicability as therapeutic agents.

microbiology↗

bioRxiv2024

Spirolactone, an unprecedented antifungal β-lactone spiroketal macrolide from Streptomyces iranensis

Fungal infections pose a great threat to public health and there are limited antifungal medicaments. Streptomyces is an important source of antibiotics, represented by the clinical drug amphotericin B. The rapamycin-producer Streptomyces iranensis harbors an unparalleled Type I polyketide synthase, which codes for a novel antifungal macrolide alligamycin A (1), the structure of which was confirmed by NMR, MS, and X-ray crystallography. Alligamycin A harbors an undescribed carbon skeleton with 13 chiral centers, featuring a ({beta}-lactone moiety, a [6,6]-spiroketal ring, and an unprecedented 7-oxo-octylmalonyl-CoA extender unit incorporated by a potential novel crotonyl-CoA carboxylase/reductase. The ali biosynthetic gene cluster was confirmed through CRISPR-based gene editing. Alligamycin A displayed profound antifungal effects against numerous clinically relevant filamentous fungi, including Talaromyces and Aspergillus species. ({beta}-Lactone ring is essential for the antifungal activity and alligamycin B (2) with disruption in the ring abolished the antifungal effect. Proteomics analysis revealed alligamycin A potentially disrupted the integrity of fungal cell walls and induced the expression of stress-response proteins in Aspergillus niger. Alligamycins represent a new class of potential drug candidate to combat fungal infections.

biochemistry↗

bioRxiv2022

Streptomyces alleviate abiotic stress in plant by producing pteridic acids

Soil microbiota can confer fitness advantages to plants and increase crop resilience to drought and other abiotic stressors. However, there is little evidence on the mechanisms correlating a microbial trait with plant abiotic stress tolerance. Here, we report that Streptomyces effectively alleviates the drought and salinity stress by producing spiroketal polyketide pteridic acid H (1) and its isomer F (2), both of which promote root growth in Arabidopsis at a concentration of 1.3 nM under abiotic stress. Pteridic acids induce stress response genes expression in salinity-stressed Arabidopsis seedlings. The bifunctional biosynthetic gene cluster of pteridic acids and antimicrobial elaiophylin is confirmed in vivo and mainly disseminated by vertical transmission which is geographically distributed in various environments. This discovery reveals a perspective for understanding plant-Streptomyces interactions and provides a promising approach for utilising beneficial Streptomyces and their secondary metabolites in agriculture to mitigate the detrimental effects of climate change.

microbiology↗