Secondary metabolites shape Streptomyces-Streptomyces interaction: Mass Spectrometry Imaging reveals lydicamycins broadly induce sporulation DOI Creative Commons
Scott A. Jarmusch, Morten Schostag, Zhijie Yang

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 2, 2024

Streptomyces are major players in soil microbiomes, however, interactions involving - rarely described. The complex developmental cycle of Streptomycetes necessitates a multi-omics approach to unravel the web information. This study resulted from observation induced sporulation between two environmental isolates same site, sp. P9-2B1 and P9-2B2. When co- cultivated on potato dextrose agar (PDA), P9-2B2 wave-like strain P9- 2B1. Using Mass Spectrometry Imaging, we revealed that suite lydicamycins, antibacterial NRPS-PKS hybrid metabolites, were present this zone. Lydicamycin deficient mutants generated using CRISPR-base editing inducible ceased, confirming their role triggering morphological differentiation. In diffusion assays, pure lydicamycin was inhibitory when added concurrently with bacterial inoculation delayed addition. Subsequent testing additional wave phenomenon, including coelicolor M145 M1146. We further evaluated temporal production lydicamycins monoculture over 10-day time scale. On PDA, detectable upon at day 4 PDA peaked 9. ISP2, minimal stable 10 days, coinciding lack sporulation. transcriptomics, observed upregulation early aerial mycelium development related genes four days into cocultivation also transitional responsible for spores Along these upregulated genes, numerous overall stress responses, specifically cell envelope responses. finding uncovered mediated by pointing potential certain groups bioactive metabolites nature.

Language: Английский

Pangenome mining of the Streptomyces genus redefines species’ biosynthetic potential DOI Creative Commons
Omkar S. Mohite, Tue Sparholt Jørgensen, Thomas Booth

et al.

Genome biology, Journal Year: 2025, Volume and Issue: 26(1)

Published: Jan. 14, 2025

Background Streptomyces is a highly diverse genus known for the production of secondary or specialized metabolites with wide range applications in medical and agricultural industries. Several thousand complete nearly genome sequences are now available, affording opportunity to deeply investigate biosynthetic potential within these organisms advance natural product discovery initiatives. Results We perform pangenome analysis on 2371 genomes, including approximately 1200 assemblies. Employing data-driven approach based similarities, was classified into 7 primary 42 Mash-clusters, forming basis comprehensive mining. A refined workflow grouping gene clusters (BGCs) redefines their diversity across different Mash-clusters. This also reassigns 2729 BGC families only 440 families, reduction caused by inaccuracies boundary detections. When genomic location BGCs included analysis, conserved structure, synteny, among becomes apparent species synteny suggests that vertical inheritance major factor diversification BGCs. Conclusions Our dataset at scale thousands genomes refines predictions using Mash-clusters as analysis. The observed conservation order BGCs’ locations shows vertically inherited. presented in-depth pave way large-scale investigations enhance our understanding genus.

Language: Английский

Citations

1
Machine learning uncovers the transcriptional regulatory network for the production host Streptomyces albidoflavus DOI Creative Commons
Mathias Jönsson, Renata Sigrist, Tetiana Gren

et al.

Cell Reports, Journal Year: 2025, Volume and Issue: 44(3), P. 115392 - 115392

Published: March 1, 2025

Highlights•Machine learning from 218 Streptomyces albidoflavus RNA-seq samples revealed 78 iModulons•The iModulons describe how the transcriptome is affected in different growth conditions•We gain insight into biosynthetic gene clusters are regulated•The available on iModulonDBSummaryStreptomyces a widely used strain for natural product discovery and production through heterologous (BGCs). However, transcriptional regulatory network (TRN) its impact secondary metabolism remain poorly understood. Here, we characterize TRN using independent component analysis RNA sequencing (RNA-seq) transcriptomes across 88 unique conditions. We identify independently modulated sets of genes (iModulons) that quantitatively diverse Our analyses reveal (1) adaptation to conditions, (2) conserved characteristics lineages, (3) activation several endogenous BGCs, including surugamide, minimycin, paulomycin, (4) inferred functions 40% uncharacterized S. genome. These findings provide comprehensive quantitative understanding TRN, offering knowledge base further exploration experimental validation.Graphical abstract

Language: Английский

Citations

0
Integrative metabolo-genomics suggests a biosynthetic pathway for tetrangulol in Streptomyces sp. KL110A DOI Creative Commons
Luisa M. Trejo-Alarcon, Carolina Cano‐Prieto, Ana Calheiros de Carvalho

et al.

World Journal of Microbiology and Biotechnology, Journal Year: 2025, Volume and Issue: 41(3)

Published: March 1, 2025

Natural products (NPs) of microbial origin are highly valued for their diverse bioactive properties. Among bacteria, Streptomyces stands out as a prolific source NPs with applications in medicine and agriculture. Recent advances metabolomics, bioinformatics well the abundance genomic data have revolutionized study NPs, enabling rapid connection biosynthetic pathways metabolites. However, discovering novel compounds from large pools genomes strains is cumbersome. Metabolo-genomics approaches promising strategies that can save time resources at initial stages natural product discovery pipeline by rapidly linking molecules genes. Here, we present characterization metabolomic profiling sp. KL110A, strain isolated rainforest soils Calakmul, Campeche Mexico. Using genome mining tools LC-MS/MS identified characterized known gene clusters (BGCs) proposed mechanism biosynthesis benz(a)anthraquinone tetrangulol. Our findings underscore relevance integrating elucidating pathways, positively contributing to field research.

Language: Английский

Citations

0
Machine Learning Uncovers the Transcriptional Regulatory Network for the Production HostStreptomyces albidoflavus DOI Creative Commons
Mathias Jönsson, Renata Sigrist, Tetiana Gren

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 10, 2024

Abstract Streptomyces albidoflavus is a popular and genetically tractable platform strain used for natural product discovery production via the expression of heterologous biosynthetic gene clusters (BGCs). However, its transcriptional regulatory network (TRN) impact on secondary metabolism poorly understood. Here we characterized TRN by applying an independent component analysis to compendium 218 high quality RNA-seq transcriptomes from both in-house public sources spanning 88 unique growth conditions. We obtained 78 independently modulated sets genes (iModulons) that quantitatively describe activity state across diverse Through analyses condition-dependent states, (i) how adapts different conditions, (ii) conduct cross-species iModulon comparison, uncovering shared features characteristics lineages, (iii) detail activation several endogenous BGCs, including surugamide, minimycin paulomycin, (iv) infer potential functions 40% uncharacterized in S. genome. Our findings provide comprehensive quantitative understanding , providing knowledge base further exploration experimental validation. Graphical

Language: Английский

Citations

0
Secondary metabolites shape Streptomyces-Streptomyces interaction: Mass Spectrometry Imaging reveals lydicamycins broadly induce sporulation DOI Creative Commons
Scott A. Jarmusch, Morten Schostag, Zhijie Yang

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 2, 2024

Streptomyces are major players in soil microbiomes, however, interactions involving - rarely described. The complex developmental cycle of Streptomycetes necessitates a multi-omics approach to unravel the web information. This study resulted from observation induced sporulation between two environmental isolates same site, sp. P9-2B1 and P9-2B2. When co- cultivated on potato dextrose agar (PDA), P9-2B2 wave-like strain P9- 2B1. Using Mass Spectrometry Imaging, we revealed that suite lydicamycins, antibacterial NRPS-PKS hybrid metabolites, were present this zone. Lydicamycin deficient mutants generated using CRISPR-base editing inducible ceased, confirming their role triggering morphological differentiation. In diffusion assays, pure lydicamycin was inhibitory when added concurrently with bacterial inoculation delayed addition. Subsequent testing additional wave phenomenon, including coelicolor M145 M1146. We further evaluated temporal production lydicamycins monoculture over 10-day time scale. On PDA, detectable upon at day 4 PDA peaked 9. ISP2, minimal stable 10 days, coinciding lack sporulation. transcriptomics, observed upregulation early aerial mycelium development related genes four days into cocultivation also transitional responsible for spores Along these upregulated genes, numerous overall stress responses, specifically cell envelope responses. finding uncovered mediated by pointing potential certain groups bioactive metabolites nature.

Language: Английский

Citations

0