What Does Ectoine Do to DNA? A Molecular-Scale Picture of Compatible Solute–Biopolymer Interactions

Abstract

Compatible solutes accumulate in the cytoplasm of halophilic microorganisms, enabling their survival in a high-salinity environment. Ectoine is such a compatible solute. It is a zwitterionic molecule that strongly interacts with surrounding water molecules and changes the dynamics of the local hydration shell. Ectoine interacts with biomolecules such as lipids, proteins, and DNA. The molecular interaction between ectoine and biomolecules, in particular the interaction between ectoine and DNA, is far from being understood. In this paper, we describe molecular aspects of the interaction between ectoine and doublestranded DNA (dsDNA). Two 20 base pairs-long dsDNA fragments were immobilized on a gold surface via a thiol-tether. The interaction between the dsDNA monolayers with diluted and concentrated ectoine solutions was examined by means of X-ray photoelectron and polarization modulation infrared reflection absorption spectroscopies (PM IRRAS). Experimental results indicate that the ability of ectoine to bind water reduces the strength of hydrogen bonds formed to the ribose-phosphate backbone in the dsDNA. In diluted (0.1 M) ectoine solution, DNA interacts predominantly with water molecules. The sugar−phosphate backbone is involved in the formation of strong hydrogen bonds to water, which, over time, leads to a reorientation of the planes of nucleic acid bases. This reorientation destabilizes the strength of hydrogen bonds between the bases and leads to a partial dehybridization of the dsDNA. In concentrated ectoine solution (2.5 M), almost all water molecules interact with ectoine. Under this condition, ectoine is able to interact directly with DNA. Density functional theory (DFT) calculations demonstrate that the direct interaction involves the nitrogen atoms in ectoine and phosphate groups in the DNA molecule. The results of the quantum-chemical calculations show that rearrangements in the ribose-phosphate backbone, caused by a direct interaction with ectoine, facilitates contacts between the O atom in the phosphate group and H atoms in a nucleic acid base. In the PM IRRA spectra, an increase in the number of IR absorption modes in the base pair frequency region proves that the hydrogen bonds between bases become weaker. Thus, a sequence of reorientations caused by interaction with ectoine leads to a breakdown of hydrogen bonds between bases in the double helix.

Electronic Properties of Protein Destabilizers and Stabilizers: Implications for Preferential Binding and Exclusion Mechanisms

“…In terms of Lewis basic macromolecules, recent articles already reported the strong binding of both stabilizers and destabilizers to negatively charged and thus Lewis basic DNA structures. ,,, Our results thus provide a rationale for these findings. In addition to electrostatic and dispersion interactions, fundamental charge transfer reactions as first-order effects significantly contribute to these observations.…”

“…In addition to electrostatic and dispersion interactions, fundamental charge transfer reactions as first-order effects significantly contribute to these observations. A recent article also highlighted the strong binding of Ect to single-stranded DNA by evaluation of the electronic properties …”

“…We are not bound by the various influences of the medium, which is particularly advantageous for the transferability of the approach to solutions with unknown dielectric constants. In addition, also, different conformational dependencies relying on the degree of hydration have been reported for Ect, which are circumvented by gas-phase calculations. − The corresponding values of E HOMO , E LUMO , and the dipole moment D for the considered species in combination with the electronegativity χ, the chemical hardness η, the electrophilicity ω, the electrofugality β E , and the nucleofugality β N are presented in Table . Further DFT calculations for a 3-isopropylacrylamide (3NIPAM) trimer as a proxy for proteins ,, with the same protocol provided values of E HOMO = –6.52 eV and E LUMO = –2.13 eV, leading to χ P = 4.33 eV and η P = 4.39 eV.…”

Biocontrol Potential of Endophytic Streptomyces malaysiensis 8ZJF-21 From Medicinal Plant Against Banana Fusarium Wilt Caused by Fusarium oxysporum f. sp. cubense Tropical Race 4

“…Other siderophore-producing rhizobacteria were also reported as biocontrol agents including Pseudomonas koreensis , Burkholderia cepacian , Rahnella aquatilis , and Bacillus subtilis ( Carmona-Hernandez et al, 2019 ; Ghazy and El-Nahrawy, 2021 ). Ectoine could interact with biomolecules such as lipids, proteins, and DNA to protect itself from environmental stresses ( Fenizia et al, 2020 ; Wittmar et al, 2020 ). Nigericin produced by endophytic S. endus OsiSh-2 exhibited remarkable antagonistic activity against rice blast disease ( Xu et al, 2017 ).…”

Utilization and accumulation of compatible solutes in Halomonas pacifica: a species of moderately halophilic bacteria isolated from a saline lake in South Libya

“…Compatible solutes, and the organisms that produce them, have attracted considerable interest in recent years [14]. Ectoine and hydroxyectoine are of particular interest, because they have particularly powerful effects in stabilizing cells and biomolecules [15,16]. They have applications in stabilizing cells against stress [17,18] and are used widely in skin care [19], with sales estimated at 15000 tonnes per annum [20], generating a market of tens of millions of US dollars per year [21].…”