A Chemo-Enzymatic Cascade Strategy for the Synthesis of Phosphatidylcholine Incorporated with Structurally Diverse FAHFAs.

Fatty acid esters of hydroxy fatty acids (FAHFAs), a newly discovered class of human endogenous complex lipids showing great promise for treating diabetes and inflammatory diseases, exist naturally in extremely low concentrations. This work reports a chemo-enzymatic approach for the comprehensive synthesis of phospholipids containing FAHFAs via sequential steps: hydratase-catalyzed hydration of unsaturated fatty acids to generate structurally diverse hydroxy fatty acids (HFAs), followed by the selective esterification of these HFAs with fatty acids mediated by secondary alcohol-specific Candida antarctica lipase A (CALA), resulting in the formation of a series of diverse FAHFA analogs. The final synthesis is completed through carbodiimide-based coupling of FAHFAs with glycerophosphatidylcholine. Optimal reaction conditions are identified for each step, and the substrate affinity of CALA, responsible for the catalytic mechanisms during FAHFA production, is evaluated through molecular docking. Compared to multistep lab-tedious chemical synthesis, this route, relying on natural building blocks and natural biocatalysts, is significantly facile, scalable, and highly selective, affording high yields (74-98 mol %) in each step for the construction of higher FAHFA-PC series (10/12/13-FAHFAs). The developed strategy aims to increase the availability of naturally occurring FAHFA species and provide the tools for the construction of versatile and novel analogs of FAHFA conjugates.

Stacked Covalent Organic Ribbons Perpendicular to Graphene Oxide Sheets; a 1D-p-2D Design for Photocatalytic Tandem Reactions.

Development of one dimensional covalent organic frameworks (1D-COFs) with potential in light absorption and catalysis is still challenging, due to their rapid interpenetration to form 2D and 3D porous structures. Here we report a successful synthesis of imine-linked 1D covalent organic ribbons (COR), using two simple linear building blocks 1,4-Benzenediamine (Bda) and [2,2'-Bipyridine]-5,5'-dicarbaldehyde (Bpy). The obtained 1D structure with nanorod morphology could keep its physicochemical characteristic properties when it is perpendicular to the surface of graphene oxide (GO) sheets (1D-p-2D structure). Due to an AB π- π stacking and efficient charge transfer between perpendicular 1D COR and GO sheets, the obtained nanocomposite showed strong visible light absorbance (400-700 nm) with coefficient of 4.400 M-1 cm-1 and decreased recombination rate of photogenerated reactive species by 92 %. The strategy of 1D-p-2D light driven system greatly enhanced the photocatalytic activity in practical applications such as both oxidation and hydrogenation tandem reactions to a rate constant of higher than 0.02 min-1 . This study presents the first case of 1D covalent organic polymers grown perpendicularly on a carbon-based layer for boosting electron mobility through the junction between the two components.

A sustainable and regioselective synthesis of Hemi-bis(monoacylglycero)phosphates and bis(diacylglycero)phosphates.

A sustainable and green approach was developed for the scalable synthesis of uncommon naturally occurring phospholipid species, Hemi-bis(monoacylglycero)phosphates (Hemi-BMPs) and bis(diacylglycero)phosphates (BDPs) via the phospholipase D (PLD) mediated transphosphatidylation. PLD from Streptomyces sp. showed great substrate promiscuity for both phospholipids from different biological sources, and alcohol donors with diverse regiochemistry; monoacylglycerols with diverse fatty acyl structures (C12-C22), affording 74-92 wt% yields in 2 h. Experimental results demonstrated that the reaction rate is rather independent of phosphatidyls but to a large extent governed by the size, shape and regiolocation of fatty acyls incorporated on the glycerol backbone, particularly for the regio-isomers of bulky diacylglycerols (Sn-1,3 or Sn-1,2), which displays great diversity. In addition, a plausible mechanism is proposed based on molecular simulations for an elaborated explanation of the reaction thermodynamic and kinetic favorability toward the synthesis of Hemi-BMPs and BDPs.

Designer phospholipids - structural retrieval, chemo-/bio- synthesis and isotopic labeling.

Phospholipids are unique and versatile molecules, essential in a variety of biological systems. Moreover, their diverse structures and amphiphilic properties endorse their indispensable and unparalleled roles in research and industrial-related applications. However, in most cases of applications, naturally occurring phospholipids are either deficit in structural variety or insufficient in quantity; therefore, novel methods must be developed for the synthesis of new molecules or modification of natural structures. To identify sustainable and environmentally friendly approaches, this work reviews the latest progress in the acquisition of structurally defined phospholipids (designer phospholipids) from natural resources, including structural retrieval, redesign and synthesis of designer phospholipids via chemo-/enzymatic approaches. This review additionally highlights the opportunity to use biological systems to direct the production of specific phospholipid species through genetic engineering via defined metabolic pathways, and functionalization of natural phospholipids through synthetic modifications: substitutions, removals or additions of specific functional groups. A particular focus is given to the establishment of chemical and biological systems for the synthesis of isotopically labelled phospholipids for biomedical applications. The application of green chemistry principles in semi-synthesis of phospholipids including extended use of greener biocatalysts and diatomaceous earth and reduced use of hazardous and toxic solvents is also summarized.

New Insights into the Interaction of Class II Dihydroorotate Dehydrogenases with Ubiquinone in Lipid Bilayers as a Function of Lipid Composition.

The fourth enzymatic reaction in the de novo pyrimidine biosynthesis, the oxidation of dihydroorotate to orotate, is catalyzed by dihydroorotate dehydrogenase (DHODH). Enzymes belonging to the DHODH Class II are membrane-bound proteins that use ubiquinones as their electron acceptors. We have designed this study to understand the interaction of an N-terminally truncated human DHODH (HsΔ29DHODH) and the DHODH from Escherichia coli (EcDHODH) with ubiquinone (Q10) in supported lipid membranes using neutron reflectometry (NR). NR has allowed us to determine in situ, under solution conditions, how the enzymes bind to lipid membranes and to unambiguously resolve the location of Q10. Q10 is exclusively located at the center of all of the lipid bilayers investigated, and upon binding, both of the DHODHs penetrate into the hydrophobic region of the outer lipid leaflet towards the Q10. We therefore show that the interaction between the soluble enzymes and the membrane-embedded Q10 is mediated by enzyme penetration. We can also show that EcDHODH binds more efficiently to the surface of simple bilayers consisting of 1-palmitoyl, 2-oleoyl phosphatidylcholine, and tetraoleoyl cardiolipin than HsΔ29DHODH, but does not penetrate into the lipids to the same degree. Our results also highlight the importance of Q10, as well as lipid composition, on enzyme binding.

Edible oleogels as solid fat alternatives: Composition and oleogelation mechanism implications.

The growing awareness of the adverse health effects of trans-fats and saturated fats are driving researchers to seek healthy alternatives. A promising strategy to structure liquid oil, called oleogelation, has been a subject of great interest. In the development of oleogels, highly unsaturated oils can be structured through different gelation mechanisms by varying structuring agents (e.g., polymeric or low molecular weight oleogelators). Due to their potential to reduce saturated fat in food products while also providing solid texture without changing the oil's chemical composition and nutritional values, oleogels have been introduced into various products (meat, spread, and confectionary) as alternatives to traditional solid fats. However, the shortcomings of oleogels cannot be ignored, such as the softer texture and the poorer plasticity than traditional solid fat. As the physicochemical properties and functionalities of oleogels are highly dependent on their composition and structuring mechanism, it is possible to obtain a product with desirable functionality by choosing a suitable oleogelator or oil phase. Thus, comprehensive and detailed knowledge regarding the role of oleoglarors, oil phase, and oleogelation mechanism on oleogelation is needed. This review primarily focuses on published information within the last decades addressing how the composition and oleogelation mechanism affect the structure and functionality of oleogels and oleogel-based products. The factors affecting the oil gelation are summarized concerning three aspects: (i) oleogelator (chemical composition and molecular structure); (ii) oil phase (TAG composition and minor component); and (iii) oleogelation mechanism. Finally, the future perspectives toward oleogels are highlighted. This review aims to deepen the understanding of oleogelation and the rational design of oleogel-based products.

Enzyme-Assisted Synthesis of High-Purity, Chain-Deuterated 1-Palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine.

1-Palmitoyl-d 31-2-oleoyl-d 32-sn-glycero-3-phosphocholine (POPC-d 63) with the palmitoyl and oleoyl chains deuterium-labeled was produced in three steps from 1-palmitoyl-2-hydroxy-sn-glycero-3-phosphocholine, deuterated palmitic acid, and deuterated oleic anhydride. Esterification at the sn-2 position was achieved under standard chemical conditions, using DMAP to catalyze the reaction between the 2-lysolipid and oleic anhydride-d 64. Complete regioselective sn-1 acyl substitution was achieved in two steps using operationally simple, enzyme-catalyzed regioselective hydrolysis and esterification to substitute the sn-1 chain for a perdeuterated analogue. This method provides chain-deuterated POPC with high chemical purity (>96%) and complete regiopurity, useful for a variety of experimental techniques. This chemoenzymatic semisynthetic approach is a general, modular method of producing highly pure, mixed-acyl phospholipids, where the advantages of both chemical synthesis (efficiency, high yields) and biocatalytic synthesis (specificity, nontoxicity) are realized.