The de novo construction of a living organism is a compelling vision. Despite the astonishing technologies developed to modify living cells, building a functioning cell "from scratch" has yet to be accomplished. The pursuit of this goal alone has─and will─yield scientific insights affecting fields as diverse as cell biology, biotechnology, medicine, and astrobiology. Multiple approaches have aimed to create biochemical systems manifesting common characteristics of life, such as compartmentalization, metabolism, and replication and the derived features, evolution, responsiveness to stimuli, and directed movement. Significant achievements in synthesizing each of these criteria have been made, individually and in limited combinations. Here, we review these efforts, distinguish different approaches, and highlight bottlenecks in the current research. We look ahead at what work remains to be accomplished and propose a "roadmap" with key milestones to achieve the vision of building cells from molecular parts.
1 November 2021 in WIREs Nanomedicine and Nanobiotechnology
Catalysis is an essential feature of living systems biochemistry, and probably, it played a key role in primordial times, helping to produce more complex molecules from simple ones. However, enzymes, the biocatalysts par excellence, were not available in such an ancient context, and so, instead, small molecule catalysis (organocatalysis) may have occurred. The best candidates for the role of primitive organocatalysts are amino acids and short random peptides, which are believed to have been available in an early period on Earth. In this review, we discuss the occurrence of primordial organocatalysts in the form of peptides, in particular commenting on reports about seryl-histidine dipeptide, which have recently been investigated. Starting from this specific case, we also mention a peptide fragment condensation scenario, as well as other potential roles of peptides in primordial times. The review actually aims to stimulate further investigation on an unexplored field of research, namely one that specifically looks at the catalytic activity of small random peptides with respect to reactions relevant to prebiotic chemistry and early chemical evolution.