Biology subjects

Martin, N. I.

Publications and source records attributed to Martin, N. I..

5 recordsLinked to original sources

bioRxiv2025

Paenitracins, a novel family of bacitracin-type nonribosomal peptide antibiotics produced by plant-associated Paenibacillus species

The growing threat of antimicrobial resistance necessitates the discovery of novel antibiotics with activity against drug-resistant pathogens. Members of the genus Paenibacillus are a rich source of nonribosomal peptides (NRPs), including well-known antibiotics such as polymyxins, paenibacterin and tridecaptins. Here we use a targeted Mass-QL-based mass spectrometry approach to identify the NRPs produced by a collection of 227 taxonomically diverse plant-associated Paenibacillus strains, providing detailed insights into their NRP-producing potential. Using MassQL to zoom in specifically on NRPs containing basic amino acids, we discovered a novel family of bacitracins, which we designated paenitracins. The paenitracins are the first bacitracin-type peptides reported in Paenibacillus, and are distinguished from canonical bacitracins by three previously unseen amino acid substitutions. The paenitracins exhibit potent activity against Gram-positive pathogens, including vancomycin-resistant Enterococcus faecium E155. Our work provides a novel metabolomics- and genomics-guided workflow for the discovery of bioactive NRPs as a strategy to prioritize natural product chemical space and accelerate antibiotic discovery. IMPORTANCEMembers of the genus Paenibacillus play an important role in soil ecology, producing a range of important nonribosomal peptides (NRPs) that protect their eukaryotic host. A collection of plant-associated Paenibacillus spp. was analyzed for their phylogenetic and metabolic diversity. We developed a novel discovery pipeline that combines feature-based molecular networking with MassQL queries to systematically prioritize bioactive NRPs containing basic amino acids. Thus we provide a comprehensive genus-wide inventory of NRPs produced by Paenibacillus spp. We thereby identified the paenitracins, a new subfamily of bacitracins active against multidrug-resistant Gram-positive pathogens. Our pipeline enables the discovery of novel peptidic natural products to accelerate the prioritization of chemical space for antibiotics.

microbiology↗

bioRxiv2025

Fork Reversal Safeguards Epigenetic Inheritance during DNA Replication Under Stress

During DNA replication, epigenetic information carried by histone modifications is faithfully propagated and re-established on sister chromatids, ensuring cell identity. Chromatin reassembly is tightly coupled to DNA replication, therefore whether and how perturbations to DNA replication affects the fidelity of epigenetic inheritance remain poorly understood. In this study, we reveal a critical role for replication fork reversal in maintaining the transmission of epigenetic information under replication stress. We identify that cells defective in fork reversal exhibit reduced nucleosome density at replication forks, accompanied by the loss of parental histones during their transfer onto nascent DNA. Mechanistically, we demonstrate that PrimPol activation leads to single-stranded DNA gaps in fork reversal deficient cells, and that subsequent PARylation (poly ADP-ribosylation) and DNA-protein crosslinking on these gaps evicts nucleosomes. Our findings demonstrate that replication fork reversal, a widespread physiological process, is not only essential for preserving genome integrity but also for safeguarding epigenetic stability.

biochemistry↗

bioRxiv2025

Antifungal biosynthesis by root-associated Streptomyces and Pseudomonas is elicited upon plant colonization

Plants are colonized by a diverse microbiome, with microorganisms residing inside and outside of plant tissues. Plants can harness the protective traits of their microbial inhabitants to ward off insect pests and fungal pathogens. However, current understanding of the role of commensal interactions on activating the desired microbial genomic traits remains limited. Here we show that biosynthesis of the antifungal 2,5-dihydro-L-phenylalanine (DHP) by the endophytic Streptomyces sp. PG2 is strongly induced upon colonization of Arabidopsis thaliana. DHP production protects the plant from infection by the fungal root pathogen Rhizoctonia solani, both in vitro and in vivo.. We identified the DHP biosynthetic gene cluster (BGC) and showed that heterologous expression of the BGC in the DHP non-producer Streptomyces coelicolor also conferred plant-inducible DHP production. The BGC was also found in plant-associated Gram-negative bacteria, and in Pseudomonas syringae FF5 we again observed strongly enhanced DHP production upon plant colonization. An ecology-inspired elicitor screen showed that L-valine and brassinosteroid hormones elicit DHP biosynthesis in the plant-beneficial Streptomyces sp. PG2, while L-valine also elicited DHP biosynthesis in S. coelicolor. In vivo experiments confirmed the stimulation of antifungal activity in Streptomyces sp. PG2 by L-valine, while brassinolide mutant plants showed reduced DHP induction. Conversely, neither L-valine nor brassinolide elicited the expression of the DHP BGC in the pathogenic P. syringae, revealing important divergence in the responses to plant signaling, which may reflect selectivity in how endosymbionts and pathogens respond to host cues. Collectively, our data demonstrate that plant colonization can elicit the biosynthetic potential of root-associated microbes, thereby enhancing plant resilience.

microbiology↗

bioRxiv2024

A new pathway in central metabolism mediates nutrient control of development and antibiotic production by Streptomyces

The amino sugar N-acetylglucosamine (GlcNAc) plays a central role in primary metabolism and is a key signaling molecule for the onset of morphological and chemical differentiation of Streptomyces. The global nutrient-sensory regulator DasR acts as the gatekeeper of development in streptomycetes, and its activity is modulated by aminosugar phosphates. Here, we report the discovery of a novel pathway in aminosugar metabolism that governs GlcNAc sensing. GlcNAc-6P is converted into a toxic metabolite via two new enzyme functions, namely dehydration of N-acetylglucosamine-6-phosphate by NagS to form 6P-Chromogen I, a reaction that has not yet been described in the textbooks, and its subsequent deacetylation by NagA producing a cytotoxic structural analogue of ribose. The latter reveals an unexpected promiscuous activity for GlcNAc-6P deacetylase NagA. The crystal structures of NagS apoenzyme and NagS in complex with its substrate GlcNAc-6P or its inhibitor 6-phosphogluconate were resolved at 2.3 [A], 2.6 [A], and 1.7 [A] resolution, respectively. Detailed in vivo and in vitro studies resolved the key residues of the NagS catalytic site. Thus, we have uncovered a novel pathway in aminosugar metabolism that sheds new light on nutrient-mediated control of development and antibiotic production in Streptomyces.

microbiology↗

bioRxiv2022

The plant stress hormone jasmonic acid evokes defensive responses in streptomycetes

Actinobacteria are prevalent in the rhizosphere and phyllosphere of diverse plant species where they help to enhance tolerance of plants against biotic and abiotic stresses. Here, we show that the plant hormones jasmonic acid (JA) and methyljasmonate (MeJA) alter growth, development and specialized metabolism of Streptomyces. Challenge of Streptomyces coelicolor with JA or MeJA led to strongly enhanced production of the polyketide antibiotic actinorhodin. JA is toxic to Streptomycetaceae, whereby members of the genus Streptacidiphilus are generally more sensitive than streptomycetes. As a defensive response, extensive amino acid conjugation of JA was observed; the most prevalent conjugation was with glutamine (Gln), while conjugates with Val, Tyr, Phe and Leu/Ile were identified after longer exposure to JA. Synthetic JA conjugates failed to activate antibiotic production and had strongly reduced toxicity, strongly suggesting that conjugation inactivates JA and serves to detoxify the hormone. Thus, for the first time we provide evidence that plant hormones modulate growth, development and secondary metabolism of streptomycetes, whereby amino acid conjugation serves as a defense strategy by the bacteria to circumvent plant hormone toxicity. IMPORTANCEMicroorganisms that live on or inside plants greatly influence plant health. Streptomycetes are considered to have an important role in defense against plant diseases, but the mechanisms through which they protect plants are currently not fully understood. It has been suggested that streptomycetes respond to changes in the plants physiology, among others by producing protective molecules; however, little is known of the signal transduction from plant to bacterium. We here demonstrate that the plant hormones jasmonic acid (JA) and methyljasmonate (MeJA) directly influence the life cycle of streptomycetes by modulating antibiotic synthesis and promoting faster development. Moreover, the plant hormones specifically stimulate the synthesis of the polyketide antibiotic actinorhodin in Streptomyces coelicolor. Jasmonic acid is then modified in the cell by amino acid conjugation, which reduces the bioactivity of the hormone and thus quenches the signal. To the best of our knowledge, this has not been reported previously. Collectively, these results suggest a relationship between plant physiological changes and the response of streptomycetes in multiple ways.

microbiology↗