Membrane Permeability of Fatty Acyl Compounds Studied via Molecular Simulation

Abstract

Interest in fatty acid-derived products as fuel and chemical precursors has grown substantially. Microbes can be genetically engineered to produce fatty acid-derived products that are able to cross host membranes and can be extracted into an applied organic overlay. This process is thought to be passive, with a rate dependent on the chemistry of the crossing compound. The relationship between the chemical composition and the energetics and kinetics of product accumulation within the overlay is not well understood. Through biased and unbiased molecular simulation, we compute the membrane permeability coefficients from production to extraction for different fatty acyl products, including fatty acids, fatty alcohols, fatty aldehydes, alkanes, and alkenes. These simulations identify specific interactions that accelerate the transit of aldehydes across the membrane bilayer relative to other oxidized products, specifically the lack of hydrogen bonds to the surrounding membrane environment. However, since extraction from the outer membrane leaflet into the organic phase is found to be rate limiting for the entire process, we find that fatty alcohols and fatty aldehydes would both manifest similar fluxes into a dodecane overlay under equivalent conditions, outpacing the accumulation of acids or alkanes into the organic phase. Since aldehydes are known to be highly reactive as well as toxic in high quantities, the findings suggest that indeed fatty alcohols are the optimal long-tail fatty acyl product for extraction.

Passive membrane transport of lignin-related compounds

“…Most compounds tested were on the higher end of this permeability spectrum, with carboxylates and glycosylated LRCs being among the least permeable compounds. Breaking down the permeabilities into a interleaflet transition/membrane crossing step (Pmc) and an extraction step (Pme ) reveals that crossing rather than extraction is typically the rate-limiting step to membrane permeation (SI Appendix, Tables S1-S3), in contrast to earlier findings for fatty acyl products or terpenoids (33,34). Only for highly processed aromatic compounds, such as benzenes or cresols, or specific LRC dimers with few hydroxy groups to retard membrane crossing (5-5 and 4-O-5 linkages), is Pmc > Pme .…”

Mechanistic Insight Into the Antifungal Effects of a Fatty Acid Derivative Against Drug-Resistant Fungal Infections

“…Interactions of surfactants with lipid membranes have been investigated in the past. Vermaas et al (2017) studied membrane permeation by alkyl fatty acids compared to alcohols, aldehydes, and alkyl chains, and their extraction into a dodecane layer using atomistic MD simulations. They observed that transfer of fatty acid and alcohol between the membrane leaflet is slower compared to the other compounds.…”

Influence of Water on the Recovery of Lube Oil Dewaxing Solvent Using P84 Polyimide Membrane: A Combination of Experiment and Molecular Simulation

“…Two factors affecting gas adsorption, free volume and intermolecular attractive energy were found; Josh et al. computed the membrane permeability coefficients of different fatty acyl products through molecular dynamics (MD). And they identified specific interactions that accelerate aldehydes transit across the membrane bilayer; Sadiye et al.…”

“…Chang et al [27] analyzed gas sorption behavior in the polyimide membrane via Monte Carlo (MC) technique. Two factors affecting gas adsorption, free volume and intermolecular attractive energy were found; Josh et al computed the membrane permeability coefficients of different fatty acyl products through molecular dynamics (MD) [28] . And they identified specific interactions that accelerate aldehydes transit across the membrane bilayer; Sadiye et al used molecular simulation techniques to gain insight on sorption induced changes in the polymer matrices [29] .…”