Research Spotlight: Halogenation-Dependent Effects of the Chlorosulfolipids of Ochromonas danica on Lipid Bilayers

Posted on January 08, 2021

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“Halogenation-Dependent Effects of the Chlorosulfolipids of Ochromonas danica on Lipid Bilayers”

Of primary interest in this article are the stereochemically complex chlorosulfolipids found in the freshwater microalga Ochromonas danica. These amphiphilic molecules are unique due to a high level of chlorination and sulfation. The major chlorosulfolipid found in O. danica is danicalipin A. Danicalipin A has six chlorines and two sulfates, all with defined stereochemistry on a linear 22-carbon chain. This molecule has remained poorly studied due to difficulty purifying it from natural resources and thus has remained a popular synthetic target. Danicalipin A is cytotoxic in humans and also plays a functional role as a component of the flagellar membrane of O. danica.

Previously it was unclear how O. danica avoids self-toxicity from danicalipin A and other chlorosulfolipids that it produces, and whether or not these molecules are an integral part of their membranes. Achieving greater insight into how these molecules form and interact with membranes would lead to a better understanding of how other amphiphilic, small molecules interact with membranes. In an attempt to elucidate these interaction mechanisms and the effects of the chlorination pattern and stereochemistry of danicalipin A on toxicity and potential functional roles, Moss and coworkers combined enantioselective chemical synthesis and membrane biophysics.

Their research concluded with a proposed model for the integration of danicalipin A with lipid bilayers. The model suggests that danicalipin A is inserted at the hydrophobic/hydrophilic interface so that the sulfates are hydrated and the hydrophobic chain is buried in the bilayer. The bilayer is thus disordered and thinned due to the distortion of the lipid tails to fill the space created by danicalipin A. This interaction causes the phosphatidylcholine substitute DPTS to fluidize and form fluid giant unilamellar vesicles (GUVs) at RT. The study also showed that halogenation of the alkyl chain had a large impact on the membrane activity of sulfolipids tested. Removing chlorine atoms from danicalipin A greatly reduced its membrane activity. They also gathered data suggesting that halosulfolipids do play a functional role in O. danica based on the growth rates of this species in media containing various concentrations of chloride. Media containing higher concentrations of chloride facilitated quicker growth and different cell densities of O. danica than the lower chloride concentration media. The mechanisms elucidated in this work may prove to be extremely useful in developing membranes with beneficial properties and membrane-altering molecules.

We appreciate Frank sending us this publication and for using Avanti’s phospholipids in his research!

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