16.14: Synthetic Biology

Synthetic biology is an interdisciplinary science that involves using principles from disciplines such as engineering, molecular biology, cell biology, and systems biology. It involves remodeling existing organisms from nature or constructing completely new synthetic organisms for applications such as protein or enzyme production, bioremediation, value-added macromolecule production, and the addition of desirable traits to crops, to name a few.

Golden rice

Golden rice is a genetically modified rice plant that produces grains rich in β-carotene - a precursor of vitamin A. Rice plants inherently possess the capability to produce β-carotene. However, production occurs only in the leaves as parts of the production pathway are turned off in the grain. Insertion of three genes encoding enzymes-phytoene synthase, phytoene desaturase, and lycopene β-cyclase into the genome of rice plants triggers the production of β-carotene in rice grains.

Artificial genome and organism

The construction of completely new synthetic genomes is relatively more complex than genome remodeling, and several efforts have been made over the years to develop this methodology gradually. In the year 2002, the first artificial viral genome for the poliovirus was synthesized. However, the major breakthrough was the synthesis of a synthetic bacterial genome of Mycoplasma genitalium in 2008. M.genitalium was selected as the organism of choice for developing this methodology because it had one of the smallest genomes with around 485 genes encoded in ~6,000,000 bp of DNA. ~100 of these genes were non-essential and were therefore eliminated to create a minimal synthetic genome.

Using the developed methodology, these researchers went a step ahead and created a synthetic single-celled organism. The genome sequence for this synthetic organism was sourced from Mycoplasma mycoides. Although the genome size of M. mycoides is larger than M.genitalium, it was chosen for this experiment due to its faster growth rate.

Partial synthesis of the genome of a yeast Saccharomyces cerevisiae in the year 2017 is the latest addition to the list of artificially synthesized genomes, and researchers are currently attempting to synthesize human cell line genomes and genomes of other plants and animals. Although synthetic biology has innumerable benefits, there are several ethical concerns surrounding it, including utilization for the development of biological weapons.

Synthetic biology is an interdisciplinary science that applies engineering principles to biology. It builds on the advances in molecular, cell, and systems biology.

Synthetic biology aims  to construct novel biological components or systems such as enzymes, cells, genetic circuits, and metabolic pathways that do not exist in nature. This can be done by redesigning the genomes of existing organisms or synthesizing completely new genomes.

Two techniques that are crucial to synthetic biology are DNA sequencing and the chemical synthesis of DNA. Sequencing helps to study the genetic material of organisms found in nature, while chemical DNA synthesis helps build newly designed sequences for testing.

Synthetic biology differs from recombinant DNA technology because it involves the use of chemically synthesized DNA sequences rather than just recombining DNA found in other organisms. The synthesized sequence could be based on sequences found in nature, or it could be completely novel.

It is also different from genetic engineering, which involves transferring individual genes from one organism or cell to another, or genome editing, which involves small changes made to the organism’s own DNA.

In genome redesign, large stretches of artificially synthesized sequences coding for multiple genes are inserted into an organism’s genome. Redesigning is usually carried out with the aim of solving specific problems.

For example, the yeast Saccharomyces cerevisiae was redesigned using bacterial and plant genes to produce a precursor to an inexpensive anti-malarial drug, artemisinin.

Synthetic biology also includes designing and artificially constructing entire genomes. For example, the bacterial genome of Mycoplasma genitalium was artificially constructed, making it the largest synthetic DNA structure.

This was done by chemically synthesizing and joining small cassettes of DNA, which were put together into subassemblies and ultimately linked to form a single genome, using homologous recombination—a DNA repair mechanism found in nature.

Additionally, scientists have also created a synthetic life form—a single-celled organism that was created using an artificially synthesized genome, the sequence of which was sourced from an organism, Mycoplasma mycoides, found in nature.