Jonathan Parra

@jonathanparra.bsky.social

Scientist ⚗️🔬. Ocean lover 🌊. Assistant Professor at University of Costa Rica 🌻. Research Associate at CENIBiot 🧬. #NaturalProducts #ChemicalEcology #DrugDiscovery https://parralab.netlify.app/

Looking for BGCs in large metagenomic datasets? Our new biorxiv preprint introduces metaSMASH, a scalable fork of antiSMASH designed specifically for metagenome-scale BGC detection and analysis : www.biorxiv.org/cgi/content/... Thanks @canerbagci.bsky.social and @kblin.bsky.social ❤️

metaSMASH: Scalable Biosynthetic Gene Cluster Detection for Large Metagenomic Assemblies

antiSMASH is widely used for biosynthetic gene cluster (BGC) detection and annotation, but its standard workflow is poorly suited to large metagenomic assemblies, where massive contig counts create severe runtime bottlenecks and complicate downstream result exploration. We present metaSMASH, a re-engineered fork of antiSMASH for metagenome-scale BGC analysis. metaSMASH preserves the original antiSMASH detection and annotation logic while introducing streaming, memory-bounded execution, record-level parallelisation, optional output filtering, and an interactive dashboard for large result sets. Across 25 benchmark metagenome datasets, metaSMASH reproduced identical BGC detection results while dramatically reducing computational cost. Relative to the default antiSMASH configuration, metaSMASH was a geometric-mean 38x faster. It also outperformed an ad hoc chunked antiSMASH workflow: in the default configuration it achieved a geometric-mean 2.9x speed-up and 1.7x lower peak memory, and with extended-analysis modules enabled it was 2.7x faster and used 3.1x less memory while completing all datasets, whereas the ad hoc workflow ran out of memory on the two largest assemblies. By substantially reducing the computational burden of large-scale metagenome analysis without sacrificing result equivalence, metaSMASH makes routine mining of assembled metagenomes more practical and provides a scalable foundation for natural product discovery from complex microbial communities. ### Competing Interest Statement The authors have declared no competing interest. German Center for Infection Research, TTU Novel Antibiotics 09.716 Volkswagen Foundation, 0072511-00

biorxiv.org

Microbes that have the greatest genomic potential for secondary metabolism tend to be multicellular. Here, we show that signatures of ancestral BGC expansions within 3 bacterial phyla and 2 fungal lineages coincide with origins of complex multicellularity [1/12] 🧵 www.nature.com/articles/s41...

Complex multicellularity is linked with expanded specialized metabolite production in microorganisms - Nature Microbiology

The evolutionary emergence of complex multicellularity in bacteria and fungi, such as the ability for mycelial growth, is strongly associated with increased genomic carriage of biosynthetic machinery ...

nature.com

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Latest from the lab and a fantastic collaboration with Eric Brown's team at @mcmasteriidr.bsky.social. Screening for new antibiotics from actinomycete extracts under nutrient-deprived conditions identifies a megacluster of synergistic antibiotics that target biotin biosynthesis. rdcu.be/fqejG

A Streptomyces megacluster encodes synergistic biotin-targeting antibiotics

Nature - In Streptomyces spp., a conserved biosynthetic gene megacluster produces an arsenal of distinct antimicrobials that converge on bacterial biotin biosynthesis as a naturally evolved...

rdcu.be

I had a great time at the International Conference on Microbial Secondary Metabolites hosted by CeMiSt, DTU. Amazing talks and discussions on microbial ecology and drug discovery. I had the opportunity to present our results on the chemical ecology of actinomycetes in coastal sediments.

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After a short hiatus from social media, I am back with some exciting news: I have recently been appointed assistant professor for Natural Product Research at the University of Vienna and have started my own research group: ZdoucLab.org!

Zdouc Lab

Microbial Natural Products Meet Data Science. The Zdouc research lab at the University of Vienna investigates naturally occurring, specialized molecules called natural products. These small molecules ...

zdouclab.org

Genome Mining-Driven Isolation of New Gromomycins and Insights into Their Mode of Action | ACS Chemical Biology pubs.acs.org/doi/full/10....

Genome Mining-Driven Isolation of New Gromomycins and Insights into Their Mode of Action

The growing threat of multidrug-resistant bacterial infections highlights the urgent need for antibiotics with novel mechanisms of action. Gromomycins, a newly identified class of triterpene antibiotics, exhibit potent activity against Gram-positive bacteria, including drug-resistant species, through a previously uncharacterized mode of action. Here, we report the discovery of a gromomycin-like biosynthetic gene cluster in the Actinoplanes genus through a genome mining approach, leading to the isolation and characterization of new bioactive derivatives that overcome resistance to clinically used drugs in vancomycin-resistant enterococci. Mechanistic studies revealed that gromomycins induce rapid potassium ion leakage and depolarization of the bacterial membrane, resulting in bactericidal activity against Staphylococcus aureus. Gromomycins disrupt the integrity of the cytoplasmic membrane, as evidenced by large pore formation, leakage of intracellular contents, and subsequent cell lysis. Supplementation with membrane lipids and fatty acids neutralized their antibacterial activity, suggesting a direct membrane-targeting mechanism, further supported by the inability to raise gromomycin resistance and their toxic effects on eukaryotic cells. Collectively, these findings deepen our understanding of gromomycin activity and demonstrate the utility of genome mining to uncover structurally novel and biologically active natural products.

pubs.acs.org