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Journal articleSun T, Sun M-L, Lin L, et al., 2026,
Combining multiplex metabolic engineering with adaptive evolution strategies for high-level succinic acid production in Yarrowia lipolytica
, Synthetic and Systems Biotechnology, Vol: 11, Pages: 48-58, ISSN: 2405-805XSuccinic acid, an essential platform chemical with extensive utility in biodegradable materials, pharmaceuticals, and the food industry, faces challenges of high energy consumption and environmental pollution in traditional chemical synthesis. Here, we employed multiplex metabolic engineering and adaptive laboratory evolution to enhance succinic acid biosynthesis in Yarrowia lipolytica. By attenuating succinate dehydrogenase (Sdh) activity, mitigating by-product accumulation, and enhancing the succinate synthesis pathway, engineered strains showed efficient succinic acid production from glycerol. The titer reached 130.99 g/L under unregulated pH conditions, translating to a yield of 0.35 g/g and a productivity of 0.70 g/(L·h). Subsequently, transporter engineering and adaptive evolution strategies were applied to enhance glucose utilization for succinic acid synthesis, yielding an evolved strain that eliminated the growth lag phase and produced 106.68 g/L succinic acid from glucose, which translated to a yield of 0.32 g/g and a productivity of 0.64 g/(L·h). Additionally, transcriptomic analysis and inverse metabolic engineering revealed that 4-hydroxyphenylpyruvate dioxygenase (4-Hppd) in the tyrosine degradation pathway partially restored the growth of Sdh-deficient strains on glucose, offering new insights for subsequent succinic acid biomanufacturing using Y. lipolytica.
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Journal articleRafieenia R, Fu J, Hapeta P, et al., 2026,
Advancing arabinose-based bioproduction in Yarrowia lipolytica by integrating metabolic engineering and adaptive laboratory evolution
, Metabolic Engineering, Vol: 94, Pages: 15-23, ISSN: 1096-7176The oleaginous yeast, Yarrowia lipolytica has gained interest as a biotechnological chassis to produce foods, chemicals, pharmaceuticals, and biofuels. To reduce production costs and sustainability, inexpensive and abundant feedstocks such as lignocellulose must be used for bioproduction. Since lignocellulosic biomass contains components that cannot be utilised by Y. lipolytica, it is important to use engineering biology to enable their utilisation. L-arabinose is the second most abundant pentose in lignocellulose after xylose. However, it has received much less attention than xylose as a bioresource. In the present study, we first engineered Y. lipolytica to grow on L-arabinose as the sole carbon source. We used several wild-type and engineered strains to express the multigene arabinose cassette. Second, we used adaptive laboratory evolution to improve the utilisation of arabinose by the engineered strains. Third, we enabled the production of β-carotene from arabinose by expressing a β-carotene cassette in the evolved strain. Using minimal YNB medium supplemented with 20 g/l of arabinose as the sole carbon source resulted in the complete utilisation of L-arabinose within 120 h. In bioreactors, a β-carotene production of 418.89 mg/l was achieved with the complete utilisation of 60 g/l of L-arabinose. This study is the first to engineer L-arabinose utilisation in Y. lipolytica, opening new avenues for biomanufacturing using alternative carbon sources.
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Journal articleWang Y, Jiang Q, Vorlaufer D, et al., 2026,
Application of vitrimer-based sizing agent onto carbon fibres through thiol-ene photo-polymerisation
, Composites Part A Applied Science and Manufacturing, Vol: 202, ISSN: 1359-835XThis work introduces photocuring as a method to apply a vitrimer-based sizing agent onto carbon fibres (CFs) via a thiol–ene reaction. The vitrimer molecule, bisphenol A glycerolate di(norbornenyl ester) (BPAGDN), was synthesised as the sizing agent. Surface treatments including oxidation and silanisation were performed on unsized AS4 CFs to graft thiol groups onto the surface. Upon UV irradiation, norbornene groups on BPAGDN reacted with surface thiol groups through a photo-initiated thiol–ene reaction, coating the CFs with BPAGDN. IR spectroscopy confirmed the epoxy–acid reaction mechanism, with full conversion achieved after 14 h. The molecular structure of BPAGDN was verified by NMR. Surface treatments led to an oxygen content increase of 5.09 %, the appearance of sulphur (1.83 %), and an increase in O’-C=O bonding by 21.42 %, as determined by XPS. The vitrimer coating increased fibre diameter from 7.04 ± 0.06 µm to 7.72 ± 0.15 µm. Mechanical properties of sized CFs remained similar to unsized CFs, though with a 26.35 % decrease in Weibull modulus. The interfacial shear strength (IFSS) of 5-min vitrimer-sized CFs increased by 24.37 % (from 66.75 MPa to 83.01 MPa), due to enhanced fibre–matrix bonding. This work demonstrates a non-destructive vitrimer sizing method using BPAGDN and UV irradiation, yielding stronger fibre–matrix interfaces.
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Journal articleMartin AK, Mercier O, Bottiger B, et al., 2026,
ISHLT Consensus Statement on the Perioperative use of ECLS in Lung Transplantation: Part III: Postoperative Considerations.
, J Heart Lung Transplant, Vol: 45, Pages: e63-e81The use of extracorporeal life support (ECLS) throughout the perioperative phase of lung transplantation requires nuanced planning and execution by an integrated team of multidisciplinary experts. To date, no multidisciplinary consensus document has examined the perioperative considerations of how to best manage these patients. To address this challenge, this perioperative utilization of ECLS in lung transplantation consensus statement was approved for development by the International Society for Heart and Lung Transplantation Standards and Guidelines Committee. International experts across multiple disciplines, including cardiothoracic surgery, anesthesiology, critical care, pediatric pulmonology, adult pulmonology, pharmacy, psychology, physical therapy, nursing, and perfusion, were selected based on expertise and divided into subgroups examining the preoperative, intraoperative, and postoperative periods. Following a comprehensive literature review, each subgroup developed recommendations to examine via a structured Delphi methodology. Following 2 rounds of Delphi consensus, a total of 22 recommendations regarding postoperative considerations for ECLS in lung transplantation met consensus criteria. These recommendations focus on the criteria for postoperative ECLS as well as select multidisciplinary team management considerations throughout the entire postoperative spectrum.
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Journal articleMartin AK, Mercier O, Fritz AV, et al., 2026,
ISHLT Consensus Statement on the Perioperative use of ECLS in Lung Transplantation: Part II: Intraoperative Considerations.
, J Heart Lung Transplant, Vol: 45, Pages: e35-e62The use of extracorporeal life support (ECLS) throughout the perioperative phase of lung transplantation requires nuanced planning and execution by an integrated team of multidisciplinary experts. To date, no multidisciplinary consensus document has examined the perioperative considerations of how to best manage these patients. To address this challenge, this perioperative utilization of ECLS in lung transplantation consensus statement was approved for development by the International Society for Heart and Lung Transplantation Standards and Guidelines Committee. International experts across multiple disciplines, including cardiothoracic surgery, anesthesiology, critical care, pediatric pulmonology, adult pulmonology, pharmacy, psychology, physical therapy, nursing, and perfusion, were selected based on expertise and divided into subgroups examining the preoperative, intraoperative, and postoperative periods. Following a comprehensive literature review, each subgroup developed recommendations to examine via a structured Delphi methodology. Following 2 rounds of Delphi consensus, a total of 39 recommendations regarding intraoperative considerations for ECLS in lung transplantation met consensus criteria. These recommendations focus on the planning, implementation, management, and monitoring of ECLS throughout the entire intraoperative period.
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Journal articlePolineni D, Davies JC, Boyd AC, et al., 2025,
Potential gene therapies for cystic fibrosis: a plain language summary for non-specialists and the lay community
, Future Rare Diseases, Vol: 5 -
Journal articleMorón-Ortiz Á, Ferrando-Marco M, León-Vaz A, et al., 2025,
Effects of lutein, phytoene and carotenoid-rich microalgal extracts on the epidermis of Caenorhabditis elegans.
, Food Chem, Vol: 497Carotenoids are widespread bioactive compounds that can accumulate in the skin. Microalgae, such as Chlorella sorokiniana and Dunaliella bardawil, are a sustainable source of natural carotenoids. This study evaluates the effect of phytoene- and lutein-rich green microalgal extracts along with pure phytoene and lutein, on the epidermis of the nematode Caenorhabditis elegans. Wild-type and sensitised mutant backgrounds were used to examine the effect of the selected carotenoids on epidermal stem cells, which differentiate to give rise to mature epidermal, neuronal, and support cell types. We also assessed their impact on cuticle integrity, the protective outer layer secreted by epidermal cells. Results revealed that phytoene-enriched microalgae at 3 μg/mL significantly increased stem cell number and improved cuticle integrity (4.4- to 12.4-fold less permeable). Our findings support a role for carotenoids in the epidermis of C. elegans, with potential implications for future developments in dermocosmetics.
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Journal articleLedesma Amaro R, 2025,
Single cell profiling framework reveals metabolic subpopulations as drivers of bioproduction heterogeneity
, Nature Communications, ISSN: 2041-1723Heterogeneity within clonal cell populations remains a critical bottleneck within bioprocess engineering, notably by undermining bioproduction yields. Efforts to mitigate its impact have, however, been hampered by technological difficulties quantifying metabolism at the single-cell level. Here, we propose a framework based on single-cell biosensor analysis that enables robust characterisation of cell's metabolic states, leveraging it to detect and isolate isogeneic heterogeneity in response to environmental perturbations and within microbial cell factories. We identify acute and gradual glucose depletion to induce differentiation of metabolically distinct subpopulations and reveal these subpopulations to exhibit differential production capabilities, with lower intracellular pH subpopulations exhibiting enhanced product accumulation within violacein-producing strains but reduced yields within lycopene-producing strains. Lastly, we highlight galactose cultivation as a method to modulate subpopulation dynamics towards higher-producing lycopene phenotypes. Altogether, our research provides insights into subpopulation differentiation and establishes promising avenues for the engineering of more robust and higher-producing strains.
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Journal articleBouchali R, Sentenac H, Bates KA, et al., 2025,
Unraveling the disease pyramid: the role of environmental micro-eukaryotes in amphibian resistance to the deadly fungal pathogen Batrachochytrium dendrobatidis.
, mSystemsThe disease pyramid conceptualizes the predictors of host infection risk, linking the host, the pathogen, environmental conditions, and both host and environmental microbiomes. However, the importance of the interaction between environmental and host-associated microbiomes in shaping infectious disease dynamics remains poorly understood. While the majority of studies have focused on bacteria, the role of micro-eukaryotes has been seldom investigated. Here, we explore three axes of the disease pyramid using an 18S rRNA gene metabarcoding approach to analyze the micro-eukaryotic assemblages of biofilm, water, and skin samples from three European amphibian species. Skin bacterial communities of the investigated amphibian populations have already been shown to be impacted by the presence of the lethal fungal pathogen Batrachochytrium dendrobatidis (Bd), with a higher abundance of protective bacteria in infected populations and a greater environmental microbial contribution to the skin microbiota in Bd-positive lakes. Here, we explored the relationships between the micro-eukaryotic skin communities of these tadpole populations with their surrounding environment. Tadpoles were sampled at 22 mountain lakes located in the Pyrenees (France), 8 of which harbored amphibian populations infected by Bd. We found that biofilms from Bd-negative lakes had higher environmental micro-eukaryotic diversity and a greater abundance of putative anti-Bd fungi, both in the environment and on the skin microbiota of Bufo spinosus and Rana temporaria, but not of Alytes obstetricans. Bayesian SourceTracker analysis further showed that the environmental contribution from biofilms to amphibian skin micro-eukaryotic assemblages was higher in Bd-positive lakes for B. spinosus and R. temporaria, but not for A. obstetricans.IMPORTANCEResearch on host-associated microbiomes and infectious diseases has mostly focused on bacteria, overlooking the potential contributions of micro-eukaryotes to infection d
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Journal articleMayer F, Sampson WW, Wloch D, et al., 2025,
Towards the efficient preparation of tough cellulose nanopapers
, CARBOHYDRATE POLYMERS, Vol: 370, ISSN: 0144-8617
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