Synthesis at the interface of virology and genetic code expansion

Abstract

How a virus efficiently invades its host cell and masterfully engineers its properties provides valuable lessons and resources for the emerging discipline of synthetic biology, which seeks to create engineered biological systems with novel functions. Recently, the toolbox of synthetic biology has also been enriched by the genetic code expansion technology, which has provided access to a large assortment of unnatural amino acids with novel chemical functionalities that can be site-specifically incorporated into proteins in living cells. The synergistic interplay of these two disciplines holds much promise to advance their individual progress, while creating new paradigms for synthetic biology. In this review we seek to provide an account of the recent advances at the interface of these two research areas.

COVID-19 vaccines: The status and perspectives in delivery points of view

“…For example, deletion of E proteins has been used as a strategy to attenuate several zoonotic coronaviruses [ 289 , 291 , 292 ]. Synthetic genome code expansion (GCE) technology for site-specific incorporation of unnatural amino acids into proteins [ 293 , 294 ] produced highly reproductive and genetically stable viruses with the ability to induce a robust antiviral response against MERS-CoV, and has also been applied to SARS-CoV-2 viral fragments [ 295 , 296 ]. Several live-attenuated virus vaccines, including one based on a RSV platform [ 297 ], are undergoing pre-clinical studies.…”

Harnessed viruses in the age of metagenomics and synthetic biology: an update on infectious clone assembly and biotechnologies of plant viruses

“…Virus containment can be regulated conditionally by supplying chemical compounds or unnatural genetic elements (Kelemen et al, 2018). Insertion of non-sense and unnatural codons into essential virus genes can condition the replication of engineered viruses to the presence of specific chemical and genetic suppressors.…”

Direct capsid labeling of infectious HIV-1 by genetic code expansion allows detection of largely complete nuclear capsids and suggests nuclear entry of HIV-1 complexes via common routes

“…We therefore established and applied a minimal invasive labeling strategy for HIV-1 CA based on genetic code expansion and click labeling. This method involves the exchange of a selected amino acid residue in the protein of interest with a non-canonical amino acid (ncAA) carrying a highly reactive bio-orthogonal functional group by a process termed amber suppression (Figure 1a); this residue is subsequently covalently coupled to a fluorophore functionalized with a cognate reaction partner (Figure 1a; Lang and Chin, 2014; Nikić and Lemke, 2015; Kelemen, Erickson and Chatterjee, 2018; Müller, Sakin and Müller, 2019; Krauskopf and Lang, 2020; de la Torre and Chin, 2021). Using this approach, we generated a CA-labeled HIV-1 derivative that largely retained infectivity; in contrast to previous approaches for direct CA labeling, our minimally modified derivative did not require complementation with wt virus.…”

“…We therefore established and applied a minimal invasive labeling strategy for HIV-1 CA based on genetic code expansion and click labeling. This method involves the exchange of a selected amino acid residue in the protein of interest with a noncanonical amino acid (ncAA) carrying a highly reactive bio-orthogonal functional group by a process termed amber suppression (Figure 1a); this residue is subsequently covalently coupled to a fluorophore functionalized with a cognate reaction partner (Figure 1a; Lang and Chin, 2014;Nikić and Lemke, 2015;Kelemen, Erickson and . CC-BY 4.0 International license perpetuity.…”