The rare sugar d-tagatose protects plants from downy mildews and is a safe fungicidal agrochemical

Abstract

The rare sugar D-tagatose is a safe natural product used as a commercial food ingredient. Here, we show that D-tagatose controls a wide range of plant diseases and focus on downy mildews to analyze its mode of action. It likely acts directly on the pathogen, rather than as a plant defense activator. Synthesis of mannan and related products of D-mannose metabolism are essential for development of fungi and oomycetes; D-tagatose inhibits the first step of mannose metabolism, the phosphorylation of D-fructose to D-fructose 6-phosphate by fructokinase, and also produces D-tagatose 6-phosphate. D-Tagatose 6-phosphate sequentially inhibits phosphomannose isomerase, causing a reduction in D-glucose 6-phosphate and D-fructose 6-phosphate, common substrates for glycolysis, and in D-mannose 6-phosphate, needed to synthesize mannan and related products. These chain-inhibitory effects on metabolic steps are significant enough to block initial infection and structural development needed for reproduction such as conidiophore and conidiospore formation of downy mildew.

The Differential Growth Inhibition of Phytophthora spp. Caused by the Rare Sugar Tagatose Is Associated With Species-Specific Metabolic and Transcriptional Changes

“…In particular, tagatose incubation increased the content of fructose and decreased the content of glucose, mannose and ribose in P. infestans, but not in P. cinnamomi. Tagatose is the C-4 epimer of fructose and it may inhibit fructose-metabolizing enzymes in P. infestans, as previously reported for the fructokinase in mammalian (Lu et al, 2008) and in Hyaloperonospora arabidopsidis (Mochizuki et al, 2020), with the consequent increase of the fructose content. On the other hand, the decrease in glucose content could be ascribed to the tagatose-depended inhibition of P. infestans β-glucosidase enzymes (Corneo et al, 2021), which are involved in polysaccharide and disaccharide hydrolysis (Saha et al, 1994).…”

“…Likewise, sugar- and growth-related genes involved in cell wall integrity and biogenesis (e.g., trehalose synthase, glucosyltransferase, glucose 4,6-dehydratases and β-glucan synthase genes) were downregulated by tagatose in P. infestans , but not in P. cinnamomi . The impact of tagatose on oomycete cell wall was previously reported in H. arabidopsidis , where tagatose inhibited the metabolism of mannan ( Mochizuki et al, 2020 ), which is an essential component of oomycete cell wall ( Melida et al, 2013 ). The alteration of cell wall integrity can negatively affect P. infestans pathogenicity ( Resjö et al, 2017 ), and genes related to virulence and infection processes, such as RxLR ( Kamoun, 2006 ), necrosis-inducing protein (NPP1) ( Qutob et al, 2002 ) and thrombospondin ( Robold and Hardham, 2005 ) were downregulated in tagatose-incubated P. infestans .…”

“…In both Phytophthora spp., some genes involved in the energy metabolism of glycolysis (e.g., phosphoglycerate mutase, glyceraldehyde-3-P dehydrogenase and pyruvate kinase) were upregulated by tagatose incubation. Tagatose was patented as glycolysis inhibitor in humans ( Kim et al, 2014 ) and showed inhibitory effects on glycolysis-related enzymes in H. arabidopsidis (fructokinase and phosphomannose isomerase) ( Mochizuki et al, 2020 ) and Escherichia coli (fructose phosphate aldolase) ( Stellmacher et al, 2016 ). As a possible consequence of glycolysis inhibition, P. infestans and P. cinnamomi upregulated a pyruvate phosphate dikinase gene (cluster UUUU) to generate pyruvate, as a bypass of pyruvate kinase in glycolysis reactions ( Judelson et al, 2009 ).…”

“…Tagatose inhibited the growth of several causal agents of plant diseases, such as Phytophthora infestans (tomato and potato late blight) ( Chahed et al, 2020 ), Plasmopara viticola (grapevine downy mildew) and Erysiphe necator (grapevine powdery mildew) ( Perazzolli et al, 2020 ), Hyaloperonospora parasitica (cabbage downy mildew) and Oidium violae (tomato powdery mildew) ( Mochizuki et al, 2020 ; Mijailovic et al, 2021 ). Tagatose showed also possible prebiotic effects on the phyllosphere microbiota and shifted the proportions of potential beneficial and potential pathogenic microorganisms by a selective nutritional or anti-nutritional effect on plant-associated microorganisms ( Perazzolli et al, 2020 ).…”

Susceptibility of Hop Cultivars and Rootstock to Downy Mildew Caused by Pseudoperonospora humuli

“…For instance, total monosaccharides decrease 200% in young compared with older rhizomes (Ryba cek, 1991). The rare sugar monosaccharide D-tagatose can disrupt the mannose metabolism of Hyaloperonospora arabidopsidis and appears to have fungicidal effects on P. cubensis (Mochizuki et al, 2020). Moreover, D-tagatose was found in root exudates of maize seedlings (Canellas et al, 2019).…”