Proliferating coacervate droplets as the missing link between chemistry and biology in the origins of life

The hypothesis that prebiotic molecules were transformed into polymers that evolved into proliferating molecular assemblages and eventually a primitive cell was first proposed about 100 years ago. To the best of our knowledge, however, no model of a proliferating prebiotic system has yet been realised because different conditions are required for polymer generation and self-assembly. In this study, we identify conditions suitable for concurrent peptide generation and self-assembly, and we show how a proliferating peptide-based droplet could be created by using synthesised amino acid thioesters as prebiotic monomers. Oligopeptides generated from the monomers spontaneously formed droplets through liquid–liquid phase separation in water. The droplets underwent a steady growth–division cycle by periodic addition of monomers through autocatalytic self-reproduction. Heterogeneous enrichment of RNA and lipids within droplets enabled RNA to protect the droplet from dissolution by lipids. These results provide experimental constructs for origins-of-life research and open up directions in the development of peptide-based materials.

Proliferating droplets formed via prebiotic polymerisation: the missing link between chemistry and biology on the origin of life

The hypothesis that prebiotic molecules were transformed into polymers that evolved into proliferating molecular assemblages and eventually a primitive cell was first proposed about a hundred years ago. However, no proliferating model prebiotic system has yet been realised because different conditions are required for polymer generation and self-assembly of polymers. In this study, we identified conditions suitable for concurrent peptide generation and self-assembly, and we showed how a proliferating peptide-based droplet could be created by using synthesised amino acid thioesters as prebiotic monomers. Oligopeptides generated from the monomers spontaneously formed droplets through liquid–liquid phase separation in water. The droplets underwent a steady growth–division cycle by periodic addition of monomers through autocatalytic self-reproduction. Heterogeneous enrichment of RNA and lipids within droplets enabled RNA to protect the droplet from dissolution by lipids. These results provide experimental platforms for origin-of-life research and open up novel directions in peptide-based material development.

Synthesis of benzyl sulfides via substitution reaction at the sulfur of phosphinic acid thioesters

An ambident electrophilicity of phosphinic acid thioesters is disclosed. Unexpected carbon–sulfur bond formation took place in the reaction between phosphinic acid thioesters and benzyl Grignard reagents to provide various benzyl sulfides.

Quantification ofN-acetylcysteamine activated methylmalonate incorporation into polyketide biosynthesis

Polyketides are biosynthesized through consecutive decarboxylative Claisen condensations between a carboxylic acid and differently substituted malonic acid thioesters, both tethered to the giant polyketide synthase enzymes. Individual malonic acid derivatives are typically required to be activated as coenzyme A-thioesters prior to their enzyme-catalyzed transfer onto the polyketide synthase. Control over the selection of malonic acid building blocks promises great potential for the experimental alteration of polyketide structure and bioactivity. One requirement for this endeavor is the supplementation of the bacterial polyketide fermentation system with tailored synthetic thioester-activated malonates. The membrane permeableN-acetylcysteamine has been proposed as a coenzyme A-mimic for this purpose. Here, the incorporation efficiency into different polyketides ofN-acetylcysteamine activated methylmalonate is studied and quantified, showing a surprisingly high and transferable activity of these polyketide synthase substrate analogues in vivo.