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.