Bentham Lab, Centre for Programmable Biological Matter, Durham University. Structural biology and de novo protein design applied to host-pathogen interactions, plant immunity, and neglected tropical d...

Modified nanopore simultaneously identifies diverse biomolecules and their modifications.

Catfish melanomas are the first example of a transmissible cancer in fish, genetic studies reveal

There’s a saying in the management world, popularized by NASA administrator Daniel Goldin in the 1990s, that the goal of technological improvements is to make products faster, better, and cheaper. Alt...

In research, work never really ends “Happy to give this presentation.” “Sure, I can take on teaching hours.” “I can do an extra side project.” “I’ll take care of this experiment over the weekend.

An exciting opportunity has arisen for a Postdoctoral Researcher to join the newly starting Schreier group at the John Innes Centre, working on cutting-edge science in the field of photosynthesis…

How to encourage better environmental practices across a department and influence the next generation of researchers

Formicamycins and their biosynthetic precursors, the fasamycins, form part of the phenylnaphthacenoid family of polyketide natural products. A recent atroposelective total synthesis of formicamycin H brought into question our original stereochemical assignment of the axially chiral linkage between C-6 and C-7. To address this, we obtained an X-ray crystal structure for formicamycin H that unambiguously confirmed our original assignment as the Sa atropisomer. X-ray structures for multiple additional fasamycins and formicamycins confirmed that this is common to all congeners. However, these studies identified a compounded error made by us whereby several structures previously reported as para-methoxy were found to have ortho-methoxy groups on the hanging E-ring. To address this for congeners that did not crystallize or gave nondiffracting crystals, we turned to the surprisingly underutilized 1,n-ADEQUATE NMR experiment. In total, we generated X-ray structures for 15 phenylnaphthacenoid metabolites and by combining these results report the corrected structures for three formicamycins, six fasamycins, and three biosynthetic lactone intermediates, noting that several revised fasamycin structures now match previously reported naphthacemycins. Our results highlight the utility of 1,n-ADEQUATE experiments for regiochemical determination in polysubstituted aromatic molecules. Moreover, our investigations uncovered a potential deracemization step during biosynthesis of the formicamycin framework.

Five tips to help you make the most of these opportunities

Since the widespread release of ChatGPT in December of 2022, AI has taken over much of the world by storm – including academia. Most of this happened with very little pushback, despite a myriad of iss...

AI Scientist, an autonomous research tool, first released in 2024, has now undergone peer review, highlighting its strengths and limitations.

Rhamnogalacturonan-II (RG-II) is considered the most complex glycan in nature. It forms part of an intricate network of complex glycans in the plant cell wall where it plays a critical role in plant growth, development and defence. It has been identified as an important nutrient source for the human gut microbiota (HGM), a key modulator of human health and disease status. Increasing evidence also suggests that RG-II can modulate plant-microbe interactions. Given its importance and potential, detailed studies of RG-IIs structure-function relationships and metabolism are required to underpin future crop-improvement strategies and to harness its benefits for plant and human health. Progress in this field is however hampered by RG-IIs structural complexity and limited access to enabling tools, in particular chemically defined RG-II-derived oligosaccharide (CDRO) substructures. Achieving targeted, efficient, and scalable production of CDROs remains a significant challenge and is indeed one of the major reasons why RG-II and glycomic research in general, significantly lag behind genomic and proteomic research. Here, we have genetically engineered as well as screened a diverse set of genetic strains, including transposon (Tn) mutants of the prominent model human gut microbe Bacteroides thetaiotaomicron (B. theta) and its gut and plant-associated relatives for new CDRO-generating and/or RG-II-utilising strains. Several CDROs, some of which had never been produced before by any other means (including chemical synthesis), where generated and characterised by a combination of high-resolution mass spectrometry (MS), enzymatic profiling and 2D-NMR. In addition to expanding the CDRO toolbox, we identified key genetic strains that will serve as a base or platform for the production of an unprecedented amount of CDROs covering the complexity and diversity of chemical modifications in RG-II. CDROs were later exploited to gain new insights into the microbial metabolism of RG-II in the human gut, revealing key aspects of its chemical structure that drive or limit its metabolism in B. theta. Notably, we generated new evidence in support of an alternative operational paradigm for polysaccharide utilisation systems that are widespread in the Bacteroidota phylum. We confirmed the presence of pathways for the metabolism of RG-II and/or RG-II core sugars D-apiose (D-Apif), and 3-deoxy-D-manno-2-octulosonic acid (D-Kdo) in aerobic plant-associated microbes including fungi and Flavobacterium spp., highlighting their potential to be exploited as cost-effective alternatives to B. theta for the generation of CDROs.

Three endoplasmic reticulum luminal mannosyltransferases ALG3, ALG9 and ALG12 catalyze the synthesis of the branched mannose core in N-glycans in four distinct steps. Now, cryo-electron microscopy str...

Transcription factors (TFs) are key regulators of expression of numerous genes. In wheat, many gene networks remain unresolved with the identification of TF target genes being p...