Latest Publications

Christophe Corre, Gideon A. Idowu, Lijiang Song, Melanie E. Whitehead, Lona M. Alkhalaf, Gregory L. Challis

The methylenomycins are highly functionalized cyclopentanone antibiotics produced by Streptomyces coelicolor A3(2). A biosynthetic pathway to the methylenomycins has been proposed based on sequence analysis of the proteins encoded by the methylenomycin biosynthetic gene cluster and the incorporation of labeled precursors. However, the roles played by putative biosynthetic enzymes remain experimentally uninvestigated. Here, the biosynthetic functions of enzymes encoded by mmyD, mmyO, mmyF, and mmyE were investigated by creating in-frame deletions in each gene and investigating the effect on methylenomycin production. No methylenomycin-related metabolites were produced by the mmyD mutant, consistent with the proposed role of MmyD in an early biosynthetic step. The production of methylenomycin A, but not methylenomycin C, was abolished in the mmyF and mmyO mutants, consistent with the corresponding enzymes catalyzing the epoxidation of methylenomycin C, as previously proposed. Expression of mmyF and mmyO in a S. coelicolor M145 derivative engineered to express mmr, which confers methylenomycin resistance, enabled the resulting strain to convert methylenomycin C to methylenomycin A, confirming this hypothesis. A novel metabolite (premethylenomycin C), which readily cyclizes to form the corresponding butanolide (premethylenomycin C lactone), accumulated in the mmyE mutant, indicating the corresponding enzyme is involved in introducing the exomethylene group into methylenomycin C. Remarkably, both premethylenomycin C and its lactone precursor were one to two orders of magnitude more active against various Gram-positive bacteria, including antibiotic-resistant Staphylococcus aureus and Enterococcus faecium isolates, than methylenomycins A and C, providing a promising starting point for the development of novel antibiotics to combat antimicrobial resistance.

Journal of the American Chemical Society, October 2025

Leila T. Alexander, Océane M. Follonier, Andriy Kryshtafovych,| Kim Abesamis, Sabrina Bibi-Triki, Henry G. Box, Cécile Breyton, Françoise Bringel, Loic Carrique, Alessio d'Acapito, Gang Dong, Rebecca DuBois, Deborah Fass, JulianaMartinez Fiesco, Daniel R. Fox, Jonathan M. Grimes, Rhys Grinter, Matthew Jenkins, Roman Kamyshinsky, Jeremy R. Keown, Gerald Lackner, Michael Lammers, Shiheng Liu, Andrew L. Lovering,Tomas Malinauskas, Benoît Masquida, Gottfried J. Palm, Christian Siebold,Tiantian Su, Ping Zhang, Z. Hong Zhou, Krzysztof Fidelis, Maya Topf, John Moult, Torsten Schwed

This article presents an in-depth analysis of selected CASP16 targets, with a focus on their biological and functional significance. The authors highlight the most relevant features of the target proteins and discuss how well these were reproduced in the submitted predictions. While the overall performance of structure prediction methods remains impressive, challenges persist, particularly in modeling rare structural motifs, flexible regions, small molecule interactions, posttranslational modifications, and biologically important interfaces. Addressing these limitations can strengthen the role of structure prediction in complementing experimental efforts and advancing both basic research and biomedical applications.

Proteins (Structure, Function, Bioinformatics), October 2025

Will Scott, Esther Ivorra-Molla, Dipayan Akhuli, Teresa Massam-Wu, Pawel K. Lysyganicz, Rylie Walsh, Matthew Parent, Jonathan Cook, Lijiang Song, Abhishek Kumar, Falk Schneider, Masanori Mishima, Allister Crow, Mohan K. Balasubramanian

Photobleaching of fluorescent proteins often limits the acquisition of high-quality images in microscopy. StayGold, a novel dimeric GFP recently monomerized through sequence engineering, addresses this challenge with its high photostability. There is now a focus on producing different colored StayGold derivatives to facilitate concurrent tagging of multiple targets. The unnatural amino acid 3-aminotyrosine has previously been shown to redshift superfolder GFP upon incorporation into its chromophore via genetic code expansion. Here, we apply the same strategy to redshift StayGold through substitution of tyrosine-58 with 3-aminotyrosine. The resultant red fluorescent protein, StayRose, shows an excitation wavelength maximum of 530 nm and an emission wavelength maximum of 588 nm. Importantly, the monomeric mStayRose retains the favorable photostability in vivo in Escherichia coli and zebrafish embryos. A high-resolution crystal structure of StayRose confirms the modified structure of the amino chromophore within an unperturbed 3D fold. Although reliant on genetic code expansion, StayRose provides an important step toward developing redshifted StayGold derivatives.

Journal of Biological Chemistry, December 2025

Piotr Walczak, Shen Li, Xumming Ji, Johannes Boltze

Central nervous system (CNS) disorders are usually characterized by a complex pathophysiology. The last issue of Neuroprotection featured reviews and research articles looking at peripheral factors such as the gut microbiome^{1, 2} or a history of pre-eclampsia³ and their impact on CNS conditions. Articles presented in the current issue of Neuroprotection will shift the focus back to the CNS but will continue to provide insights from recent research that help to better understand the pathophysiological complexity of CNS conditions.

Neuroinflammation is known to be a hallmark and major contributor to many CNS diseases. It comprises both peripheral and central immune cells and can be modulated by frequent comorbidities such as hypertension.⁴ Moreover, neuroinflammatory processes can involve cell populations not primarily characterized as immune cells. Psychiatric conditions, including major depressive disorders (MDD), are increasingly recognized to be linked to neuroinflammation⁵ but also to systemic comorbidities, stress and aging. A better understanding of neuroinflammatory processes in the context of psychiatric conditions may help to identify novel therapeutic targets for better and potentially causal treatment strategies.

Neuroprotection, September 2025

Laurence Hand, Mark C.J. Day, Carol Nichols, Hendrik Schäfer, Samantha Marshall, Gary D. Bending

Laboratory soil biodegradation studies required for approval of crop protection products (CPPs) are performed under continuous darkness, nullifying any potential contributions of algal and moss dominated biological soil crusts (BSC). There is growing evidence for metabolism of CPPs by phototrophic microorganisms under laboratory conditions, but limited data is available under field conditions. In this study we investigated the impact of the BSC on the fate of two ¹⁴C-fungicides under semi-field conditions using different light filters to alter formation of the BSC by exclusion/transmission of UV and photosynthetically active (PAR) wavelengths. Attenuation of PAR light significantly reduced formation of a BSC, which resulted in a significant slowing of the dissipation of benzovindiflupyr, which is known to be susceptible to phototrophic metabolism in aquatic systems, with 12–14 % more parent compound remaining at the end of the study when BSC development was impeded. For paclobutrazol, however, no significant difference in dissipation rate was observed. For both compounds there was significantly less non-extractable residue (NER) formation when BSC development was impeded (4–9 % reduction). Additionally, for both fungicides, the presence of a viable BSC resulted in 10–20 % more movement through the surface 5 mm of the soil, although this effect was limited to the period immediately after application and was likely due to increased porosity of the surface layer. This study confirms that the presence of phototrophs can significantly impact the environmental fate of CPPs on the surface of agricultural fields, either directly through metabolism or indirectly by altering the properties of the surface layer.

Science of The Total Environment November 2025

Dion Garrett, Graham Teakle, Rosemary Collier, James R Bell, Ramiro Morales-Hojas

Nasonovia ribisnigri (Mosley) is a severe aphid pest of outdoor lettuce, and the combination of sporadic and unpredictable colonization on outdoor lettuce, along with the breakdown of cultivar resistance, has left few effective control methods. The population structure (spatially and temporally) of N. ribisnigri is currently unknown in England, and therefore microsatellite markers were designed to estimate the impacts of host plant selection pressure (including host plant resistance) and environmental change. Biological samples collected between 2003 and 2020 from 10 sites across England were typed with microsatellite markers. The analysis of 8 microsatellites indicated a clear east-west divide between N. ribisnigri populations, which corresponds with current outdoor lettuce cultivation distribution in England, one of the aphid's summer hosts. Analysis of gene flow indicated that aphids did not leave the eastern region; instead, there was strong evidence for aphids migrating from the West into the secondary host eastern region, possibly from the winter host (Ribes spp.) in Spring. This result suggests that although N. ribisnigri has the potential for long-distance migration, strong ties to the summer host (lettuce) determine migratory behavior at the population level. N. ribisnigri are mostly holocyclic and show a high level of inbreeding. Long-term trends revealed relatively stable populations, despite a recent breakdown of host plant resistance and other environmental changes, including favorable temperatures. The geographic and temporal structure of the N. ribisnigri population is discussed in relation to future pest management strategies.

Journal of Insect Science October 2025