1.1,5-Anhydro-D-fructose: A natural antibiotic that inhibits the growth of gram-positive bacteria and microbial biofilm formation to prevent nosocomial infection.
Meng X1, Kawahara KI, Miyanohara H, Yoshimoto Y, Yoshinaga K, Noma S, Kikuchi K, Morimoto Y, Ito T, Oyama Y, Yoshinaga N, Shrestha B, Chandan B, Mera K, Tada KI, Miura N, Ono Y, Takenouchi K, Maenosono R, Nagasato T, Hashiguchi T, Maruyama I. Exp Ther Med. 2011 Jul;2(4):625-628. Epub 2011 Apr 1.
Nosocomial infections caused by microbial opportunistic infections or microbial biofilms may occur during hospitalization and increase patient morbidity, mortality and health care costs. Artificial antibiotic agents were initially used to prevent infection; however, the high prevalence of nosocomial infections has resulted in their excessive use, which has led to microbial resistance to these agents. The increase in microbial resistance to antibiotics and the development of antibiotic agents may be the cause of the production of other microbial resistance. Thus, natural compounds that have no adverse side effects would be a preferred treatment modality. Recently, the monosaccharide 1,5-anhydro-D-fructose (1,5-AF), a natural plant compound derived from starch, has been found to have multifunctional properties, including antioxidant, antiplatelet aggregation by thrombin and anti-inflammatory activities. The results of the present study demonstrate that 1,5-AF suppressed the growth of coagulase-negative staphylococci on the hands as well as the growth of Staphylococcus epidermidis, which is a cause of opportunistic infections.
2.1,5-anhydro-D-fructose and its derivatives: biosynthesis, preparation and potential medical applications.
Fiskesund R1, Abeyama K, Yoshinaga K, Abe J, Yuan Y, Yu S. Planta Med. 2010 Oct;76(15):1635-41. doi: 10.1055/s-0030-1250120. Epub 2010 Jul 19.
1,5-Anhydro-D-fructose (AF) was first found in fungi and red algae. It is produced by the degradation of glycogen, starch and maltosaccharides with α-1,4-glucan lyase (EC 18.104.22.168). In vivo, AF is metabolized to 1,5-anhydro-D-glucitol (AG), ascopyrone P (APP), microthecin and other derivatives via the anhydrofructose pathway. The genes coding for the enzymes in this pathway have been cloned, enabling the large-scale production of AF and related products in a cell-free reactor. The possible applications of these products in medicine have been evaluated using both in vitro and in vivo systems. Thus AF is a useful anticariogenic agent as it inhibits the growth of the oral pathogen Streptococcus mutans, impairing the production of plaque-forming polysaccharides and lactic acid. AF also shows anti-inflammatory and anticancer effects. AG is used as a diabetic marker for glycemic control. AG also stimulates insulin secretion in insulinoma cell lines.
3.Production of 1,5-anhydro-d-fructose by an α-glucosidase belonging to glycoside hydrolase family 31.
Maneesan J1, Matsuura H, Tagami T, Mori H, Kimura A. Biosci Biotechnol Biochem. 2014;78(12):2064-8. doi: 10.1080/09168451.2014.943651. Epub 2014 Aug 5.
α-1,4-Glucan lyases [glycoside hydrolase family (GH) 31] catalyze an elimination reaction to form 1,5-anhydro-d-fructose (AF), while GH31 α-glucosidases normally catalyze a hydrolytic reaction. We determined that a small amount of AF was produced by GH31 Aspergillus niger α-glucosidase from maltooligosaccharides by elimination reaction, likely via an oxocarbenium ion intermediate.
4.The structure of substrate-free 1,5-anhydro-D-fructose reductase from Sinorhizobium meliloti 1021 reveals an open enzyme conformation.
Schu M1, Faust A, Stosik B, Kohring GW, Giffhorn F, Scheidig AJ. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2013 Aug;69(Pt 8):844-9. doi: 10.1107/S1744309113019490. Epub 2013 Jul 27.
1,5-Anhydro-D-fructose (1,5-AF) is an interesting building block for enantioselective and stereoselective organic synthesis. Enzymes acting on this compound are potential targets for structure-based protein/enzyme design to extend the repertoire of catalytic modifications of this and related building blocks. Recombinant 1,5-anhydro-D-fructose reductase (AFR) from Sinorhizobium meliloti 1021 was produced in Escherichia coli, purified using a fused 6×His affinity tag and crystallized in complex with the cofactor NADP(H) using the hanging-drop technique. Its structure was determined to 1.93 Å resolution using molecular replacement. The structure displays an empty substrate-binding site and can be interpreted as an open conformation reflecting the enzyme state shortly after the release of product, presumably with bound oxidized cofactor NADP⁺. Docking simulations indicated that amino-acid residues Lys94, His151, Trp162, Arg163, Asp176 and His180 are involved in substrate binding, catalysis or product release.