In recent years, considerable effort has been devoted to the preparation of artificial nanotubular materials. One of the most successful approaches for the construction of noncovalently bonded nanotube entities is the self-assembly of cyclic polypeptides in stacks that are stabilized by hydrogen bonds. This tutorial review covers the history and current situation for synthetic organic nanostructures obtained from self-assembling cyclic peptides. In particular, we describe the evolution to cyclic peptides that not only allow the modification of the outer surface but also the inner cavity by paying special attention to peptide rings that contain cyclic γ-amino acids. In this respect, we describe the synthesis, properties and application of a new class of homo- and heterodimeric supramolecular assemblies that are precursors of cyclic α,γ-peptide nanotubes.

All living cells consist of membrane compartments, which are mainly composed of phospholipids. Phospholipid synthesis is catalyzed by membrane-bound enzymes, which themselves require pre-existing membranes for function. Thus, the principle of membrane continuity creates a paradox when considering how the first biochemical membrane-synthesis machinery arose and has hampered efforts to develop simplified pathways for membrane generation in synthetic cells. Here, we develop a high-yielding strategy for de novo formation and growth of phospholipid membranes by repurposing a soluble enzyme FadD10 to form fatty acyl adenylates that react with amine-functionalized lysolipids to form phospholipids. Continuous supply of fresh precursors needed for lipid synthesis enables the growth of vesicles encapsulating FadD10. Using a minimal transcription/translation system, phospholipid vesicles are generated de novo in the presence of DNA encoding FadD10. Our findings suggest that alternate chemistries can produce and maintain synthetic phospholipid membranes and provides a strategy for generating membrane-based materials.

This tutorial review covers recently developed technologies employed for chemical synthesis, derivatization and analysis of lipids.

Significance: Organelles spatially and temporally orchestrate biochemical reactions in a cell to a degree of precision that is still unattainable in synthetic reaction systems. Additionally, organelles such as the endoplasmic reticulum (ER) contain highly interconnected and dense membrane networks that provide large reaction spaces for both transmembrane and soluble enzymes. We present lipid sponge droplets to emulate the functions of organelles such as the ER. We demonstrate that lipid sponge droplets can be programmed to internally concentrate specific proteins, to host and accelerate biochemical transformations, and to rapidly and reversibly sequester and release proteins to control enzymatic reactions. The self-assembled and programmable nature of lipid sponge droplets will facilitate the integration of complex functions for bottom-up synthetic biology.