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How non-canonical amino acids will transform healthcare and industry

Constructive Bio

Programmable Biomolecules of the Future

DNA sequencing has allowed us to read and study the code of life, creating a $28 billion dollar industry.

Now, synthetic genomics (DNA writing at genome scale) is an emerging field giving scientists and synthetic biologists unprecedented access to interrogate and explore the central dogma at the core of biology.

Read on to learn how advances in the engineering biology toolkit are enabling new solutions at pace and have potential to transform the bio revolution.

The Genome Synthesis Revolution

DNA is the genetic blueprint of life, carrying the fundamental instructions for an organism to develop and function. These instructions are read by cellular machines that translate the DNA code into defined protein sequences; this process is known as the central dogma.


Reprogramming Life

It is widely hypothesized that removing cellular transfer RNAs (tRNAs)—making their
cognate codons unreadable—might create a genetic firewall to viral infection and enable sense codon reassignment. However, it has been impossible to test these hypotheses. In this work, following synonymous codon compression and laboratory evolution in Escherichia coli,
we deleted the tRNAs and release factor 1, which normally decode two sense codons and
a stop codon; the resulting cells could not read the canonical genetic code and were completely resistant to a cocktail of viruses. We reassigned these codons to enable the efficient synthesis of proteins containing three distinct noncanonical amino acids. Notably, we demonstrate the facile reprogramming of our cells for the encoded translation of diverse noncanonical heteropolymers and macrocycles.

Science

Sense codon reassignment enables viral resistance and encoded polymer synthesis

Refactored genetic codes enable bidirectional genetic isolation

The encoded biosynthesis of proteins provides the ultimate paradigm for high-fidelity synthesis of long polymers of defined sequence and composition, but it is limited to polymerizing the canonical amino acids. Recent advances have built on genetic code expansion — which commonly permits the cellular incorporation of one type of non-canonical amino acid into a protein — to enable the encoded incorporation of several distinct non-canonical amino acids. Developments include strategies to read quadruplet codons, use non-natural DNA base pairs, synthesize completely recoded genomes and create orthogonal translational components with reprogrammed specificities. These advances may enable the genetically encoded synthesis of non-canonical biopolymers and provide a platform for transforming the discovery and evolution of new materials and therapeutics.

Scientific Publications[ 6 ]

Programmable Biomolecules of the Future

The Genome Synthesis Revolution

Reprogramming Life

Sense codon reassignment enables viral resistance and encoded polymer synthesis

Refactored genetic codes enable bidirectional genetic isolation

Reprogramming the genetic code

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Scientific Publications[ 6 ]

Programmable Biomolecules of the Future

The Genome Synthesis Revolution

Reprogramming Life

Sense codon reassignment enables viral resistance and encoded polymer synthesis

Refactored genetic codes enable bidirectional genetic isolation

Reprogramming the genetic code

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