Module 1 Overview

The E.ncapsulator has been designed to produce and deliver polypeptides (amino acid polymers) to the intestine. Module 1 encompasses the polypeptide production phase. During this period, our polypeptide of interest is synthesised at a rate sufficient to faciliate its accumulation inside the cell.

Polypeptides are classidied according to their size and functional properties. A peptide is a short chain assembled from a small number of amino acids. Enzymes on the other hand are much larger and serve catalyse reactions.

Do demonstrate The E.ncapsulator's versatility, we have chosen to showcase it with both enzymes and peptides. These two classes of polypeptide have very different properties that we have considered and catered for in The E.ncapsulator's design.

Peptide Delivery

While a few peptide drugs can be taken orally, many are suseptible to breakdown in the stomach making them suitable candidates for encapsulation. To achieve peptide compatibilty, it was necessary to equip The E.ncapsulator with a special mechanism that facilaites peptide synthesis.

Polypeptide synthesis ALWAYS begins with the amino acid methionine. However, polypeptides are often chopped up in a controlled manner to produce a smaller functional peptide. These functional peptides often do not begin with the amino acid methionine. Therefore, if we wanted to produce peptides without having to progress down a lengthy series of cleavages, it would be wise to insert a methionine residue at the start of the peptide. Of course, this could inhibit peptide functionality. To get around this problem, we have developed a linker region that begins with methionine but is selectivly cleaved in the intestine to yield the functional peptide. This linker region is compatible with every polypeptide that does not begin with methionine.

Peptides = synthesis & selective protease protection

• Protein value = +++++++++ = first iGEM entry to provide a solution for mental issues = pain, arousal, depression

• Innovation = Generic linker gets around expensive peptide synthesis. Capsule protects from stomach proteases.

Enzymes = acid protection for 3d conformation

• Protein value = PAH = metabolic subcontraction from liver. Treatment for a genetic disease.

• Innovation = SDR for protease resistance

• Protein value = Cellulase = increase microbiome functionality

Although The E.ncapsulator is designed to be versatile with regard to which protein is to be produced, we have chosen two enzymes as demonstration, phenylalanine hydroxylase and cellulase.

Cellulase

Cellulose is a compound that is abundant in the human diet - it is what is commonly referred to as 'dietary fibre.' However, the human body is unable to degrade cellulose into glucose naturally, as it lacks the enzymes required to break down this fibrous material.

Cellulase is an enzyme that breaks down cellulose to glucose. By engineering The E.ncapsulator to produce this enzyme and delivering it to the small intestine, we would give the consumer the ability to digest dietary fibre. This would allow more energy and nutrients to be extracted from food; that which was previously unavailable.

More information on cellulase can be found here

Phenylalanine Hydroxylase

Phenylketonuria is a digestive disorder caused by an inability of the body to break down the amino acid phenylalanine. The amino acid accumulates in the blood, and can cause serious health problems for afflicted individuals. Current treatments for the condition revolve around following a strict very low protein diet.

Phenylalanine Hydroxylase (PAH) is an enzyme that breaks down the amino acid phenylalanine into tyrosine. By introducing this enzyme into the digestive system with The E.ncapsulator's unique drug delivery mechanism, we hope to treat the sufferers of PKU.

To find out more about phenylketonuria and PAH, click here.