Structural and electronic determinants of lytic polysaccharide monooxygenase reactivity on polysaccharide substrates

Lytic polysaccharide monooxygenases (LPMOs) are industrially important copper-dependent enzymes that oxidatively cleave polysaccharides. Here we present a functional and structural characterization of two closely related AA9-family LPMOs from Lentinus similis (LsAA9A) and Collariella virescens (CvAA9A). LsAA9A and CvAA9A cleave a range of polysaccharides, including cellulose, xyloglucan, mixed-linkage glucan and glucomannan. LsAA9A additionally cleaves isolated xylan substrates. The structures of CvAA9A and of LsAA9A bound to cellulosic and non-cellulosic oligosaccharides provide insight into the molecular determinants of their specificity. Spectroscopic measurements reveal differences in copper co-ordination upon the binding of xylan and glucans. LsAA9A activity is less sensitive to the reducing agent potential when cleaving xylan, suggesting that distinct catalytic mechanisms exist for xylan and glucan cleavage. Overall, these data show that AA9 LPMOs can display different apparent substrate specificities dependent upon both productive protein–carbohydrate interactions across a binding surface and also electronic considerations at the copper active site

Fungal Enzymes and Yeasts for Conversion of Plant Biomass to Bioenergy and High-Value Products

Fungi and fungal enzymes play important roles in the new bioeconomy. Enzymes from filamentous fungi can unlock the potential of recalcitrant lignocellulose structures of plant cell walls as a new resource, and fungi such as yeast can produce bioethanol from the sugars released after enzyme treatment. Such processes reflect inherent characteristics of the fungal way of life, namely, that fungi as heterotrophic organisms must break down complex carbon structures of organic materials to satisfy their need for carbon and nitrogen for growth and reproduction. This chapter describes major steps in the conversion of plant biomass to value-added products. These products provide a basis for substituting fossil-derived fuels, chemicals, and materials, as well as unlocking the biomass potential of the agricultural harvest to yield more food and feed. This article focuses on the mycological basis for the fungal contribution to biorefinery processes, which are instrumental for improved resource efficiency and central to the new bioeconomy. Which types of processes, inherent to fungal physiology and activities in nature, are exploited in the new industrial processes? Which families of the fungal kingdom and which types of fungal habitats and ecological specializations are hot spots for fungal biomass conversion? How can the best fungal enzymes be found and optimized for industrial use? How can they be produced most efficiently-in fungal expression hosts? How have industrial biotechnology and biomass conversion research contributed to mycology and environmental research? Future perspectives and approaches are listed, highlighting the importance of fungi in development of the bioeconomy

Antibody decay, T cell immunity and breakthrough infections following two SARS-CoV-2 vaccine doses in inflammatory bowel disease patients treated with infliximab and vedolizumab

AbstractAnti tumour necrosis factor (anti-TNF) drugs increase the risk of serious respiratory infection and impair protective immunity following pneumococcal and influenza vaccination. Here we report SARS-CoV-2 vaccine-induced immune responses and breakthrough infections in patients with inflammatory bowel disease, who are treated either with the anti-TNF antibody, infliximab, or with vedolizumab targeting a gut-specific anti-integrin that does not impair systemic immunity. Geometric mean [SD] anti-S RBD antibody concentrations are lower and half-lives shorter in patients treated with infliximab than vedolizumab, following two doses of BNT162b2 (566.7 U/mL [6.2] vs 4555.3 U/mL [5.4], p &lt;0.0001; 26.8 days [95% CI 26.2 – 27.5] vs 47.6 days [45.5 – 49.8], p &lt;0.0001); similar results are also observed with ChAdOx1 nCoV-19 vaccination (184.7 U/mL [5.0] vs 784.0 U/mL [3.5], p &lt;0.0001; 35.9 days [34.9 – 36.8] vs 58.0 days [55.0 – 61.3], p value &lt; 0.0001). One fifth of patients fail to mount a T cell response in both treatment groups. Breakthrough SARS-CoV-2 infections are more frequent (5.8% (201/3441) vs 3.9% (66/1682), p = 0.0039) in patients treated with infliximab than vedolizumab, and the risk of breakthrough SARS-CoV-2 infection is predicted by peak anti-S RBD antibody concentration after two vaccine doses. Irrespective of the treatments, higher, more sustained antibody levels are observed in patients with a history of SARS-CoV-2 infection prior to vaccination. Our results thus suggest that adapted vaccination schedules may be required to induce immunity in at-risk, anti-TNF-treated patients.</jats:p