Abstract
Iron dextran is a common anti-anemia drug, and it requires low molar mass dextran as substrate. In this work, we selected 11 amino acid residues in domain A/B of DSR-MΔ2 within a 5-angstrom distance from sucrose for site-directed mutagenesis by molecular docking. Mutation of Q634 did not affect the enzyme catalytic activity, but showed an obvious impact on the ratio of low molecular weight dextran (L-dextran, 3,000–5,000 Da) and relatively higher molecular weight dextran (H-dextran, around 10,000 Da). L-dextran was the main product synthesized by DSR-MΔ2 Q634A, and its average molecular weight was 3,951 Da with a polydispersity index <1.3. The structural characterization of this homopolysaccharide revealed that it was a dextran, with 86.0% α(1→6) and 14.0% α(1→4) glycosidic linkages. Moreover, L-dextran was oxidized with NaOH and chelated with ferric trichloride, and an OL-dextran-iron complex was synthesized with a high iron-loading potential of 33.5% (w/w). Altogether, mutation of amino acids near the sucrose binding site of dextransucrase can affect the chain elongation process, making it possible to modulate dextran size.
Highlights
Dextran is a homopolysaccharide generally composed of α-1,6-glycosidic linkage and occasionally branched with α-1,2, α-1,3, and α-1,4-glycosidic linkages, and it is mainly synthesized with sucrose as substrate by dextransucrase from Streptococcus, Lactobacillus, or Leuconostoc (Leemhuis, et al, 2013)
In order to study how these amino residues regulated the synthesis of dextran, site-directed mutagenesis was carried out with the aim of obtaining a series of mutants
Dextransucrase catalyzes the production of dextran using sucrose as sole substrate, and DSR-MΔ2 is one of the dextransucrases that can directly catalyze the synthesis of low molecular dextran
Summary
Dextran is a homopolysaccharide generally composed of α-1,6-glycosidic linkage and occasionally branched with α-1,2, α-1,3, and α-1,4-glycosidic linkages, and it is mainly synthesized with sucrose as substrate by dextransucrase from Streptococcus, Lactobacillus, or Leuconostoc (Leemhuis, et al, 2013). Low molar mass dextran has received wide attention due to its biological activities including its antioxidant, immunomodulatory, and antimicrobial properties (Moreno-Mendieta et al, 2017; Xia et al, 2021). Iron dextran is a complex synthesized with low molar mass dextran and ferric oxyhydroxide, and it is a common anti-anemia drug that is mainly used to treat iron-deficiency anemia (Liu et al, 2019).
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
