The Wonders of Left-Handed Proteins.

It’s an unnatural partnering – an enzyme normally found in the bacteria of our intestines, and one that makes components of proteins for a soil microbe. Together, they have been harnessed to create high-value ingredients for antibiotics and antivirals – and make them greener, cleaner, and cheaper.

UCL’s interdisciplinary team of Biocatalysis integrated with Chemistry and Engineering, BiCE, started with these chemical converters from different bugs and tailored them into custom miniature machinery. Their biological workhorses are capable of making chemicals very useful to the pharmaceutical industry, because of a peculiarity of life’s proteins – they are left-handed.

Two molecules can be made of exactly the same atoms and be identical chemically, but if they are mirror images of each other living systems process them differently. If chemical methods are used to make the molecules used in drugs, equal amounts of left and right handed molecules result – and half of them are useless. However, if molecules useful in pharmaceuticals are made using biological methods, only molecules with the right handed-ness are produced. This is obviously much more efficient because you only make what you need. Manufacturing using organic life forms as part of the process is also much more eco-friendly as it doesn’t require hazardous or expensive chemicals.

UCL Biochemical Engineering had a wide library of organic life forms and their molecular machinery to make use of, thanks to work done by UCL Structural and Molecular Biology in producing, isolating and characterising hundreds of potentially useful naturally occurring enzymes. By starting from this natural tool-kit and tweaking the order in which the enzymes work and the details of what they do, they could use their transformative properties to produce a range of aminodiols, a key ingredient in manufacturing antibiotics and antivirals. Future work hopes to adapt these biological alchemists so that they can create pharmaceutical ingredients starting from a base of waste biomass.

Once living bacteria were doing the synthesis, the scientists began to work on improving the yield to an economically viable level. The cheaper the chemical is, the more available it will be and the greater the effect it will have in the world. By using robotic automation of small-scale processing, which can be easily scaled up for industrial production, they optimized this process so it could be done on massive scales. This work will reduce the cost of manufacturing life-changing drugs for pharmaceuticals companies, the care givers who administer them, and patients.