Abstract
SummaryBiology is an analytical and informational science that is becoming increasingly dependent on chemical synthesis. One example is the high‐throughput and low‐cost synthesis of DNA, which is a foundation for the research field of synthetic biology (SB). The aim of SB is to provide biotechnological solutions to health, energy and environmental issues as well as unsustainable manufacturing processes in the frame of naturally existing chemical building blocks. Xenobiology (XB) goes a step further by implementing non‐natural building blocks in living cells. In this context, genetic code engineering respectively enables the re‐design of genes/genomes and proteins/proteomes with non‐canonical nucleic (XNAs) and amino (ncAAs) acids. Besides studying information flow and evolutionary innovation in living systems, XB allows the development of new‐to‐nature therapeutic proteins/peptides, new biocatalysts for potential applications in synthetic organic chemistry and biocontainment strategies for enhanced biosafety. In this perspective, we provide a brief history and evolution of the genetic code in the context of XB. We then discuss the latest efforts and challenges ahead for engineering the genetic code with focus on substitutions and additions of ncAAs as well as standard amino acid reductions. Finally, we present a roadmap for the directed evolution of artificial microbes for emancipating rare sense codons that could be used to introduce novel building blocks. The development of such xenomicroorganisms endowed with a ‘genetic firewall’ will also allow to study and understand the relation between code evolution and horizontal gene transfer.
Highlights
Genetic code engineering respectively enables the redesign of genes/genomes and proteins/proteomes with non-canonical nucleic (XNAs) and amino (ncAAs) acids
We believe that the experimental evolution of strains with non-canonical amino acids (ncAAs) will allow the development of ‘genetic firewall’ that can be used for enhanced biocontainment and for studying horizontal gene transfer
These efforts could allow the production of new-to-nature therapeutic proteins and diversification of difficult-to-synthesize antimicrobial compounds for fighting against ‘super’ pathogens (McGann et al, 2016)
Summary
Genetic code engineering respectively enables the redesign of genes/genomes and proteins/proteomes with non-canonical nucleic (XNAs) and amino (ncAAs) acids. The second major area concerns engineering the genetic code of proteins and proteomes with non-canonical amino acids (ncAAs) (Bacher et al, 2004; Budisa, 2004). Introducing new functional members of XNA into either DNA or RNA and ncAAs into proteins breaks the universality of the genetic code of living organisms, alienating these from other natural life forms (Budisa, 2014).
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