I’ve looked at next generation sequencing technologies on here before, in the context of identifying those genes which are unique to Alzheimer’s patients to help develop genetic screens for early detection. I’ve also looked at how a microorganism’s metabolic pathways can be hijacked and rerouted to produce new biofuels. Well researchers from Canada have begun to explore how these two efforts will collide and offer advice on how to approach this interdisciplinary crossroads.
The article, published in July 2013 in Journal of Biotechnology, looks at how the recent leaps forward in sequencing capabilities could affect biosynthesis of unique plant products. These products could be anything from chemicals used in fragrances to flavors to valuable and highly potent antibiotics. Regardless of their use though, access to these compounds has always been limited by how quickly and sustainably the plants in question can be grown. So, as with the fuel alternatives I’ve looked at before, scientists are trying to engineer microorganisms capable of producing these valuable but rare substances.
With next generation sequencing technology, researchers can examine the entirety of a plant’s (or any other organism’s) transcriptome, those genes which are actually expressed within the organism’s genome. This is done by isolating messenger RNA, or mRNA, which moves from the nucleus to ribosomes for protein formation. Thus, by sequencing mRNA, we can look at only those genes which are actually transcribed. This helps to create a more complete picture of the steps involved in these unique metabolic processes, thus allowing researchers to more accurately recreate them in another, more easily maintained organism.
The issue is that a large number of these incredibly desirable compounds are found in what are called non-model organisms, that is, these plants have not been used as a model for understanding basic, universal mechanisms of plant life. Those organisms which are “models” are heavily studied and their genomes have, as a general rule, already been sequenced. If a model organism were being used, then the transcriptome could be aligned with the genome to trace the metabolic steps from gene all the way to wonder drug. Without this though, researchers must create a “de novo” transcriptome, which seeks to characterize and organize the large number of expressed genes without a complete genome. Understanding how these gene products are connected and which ones are actually relevant to the substance in question is much more difficult this way, as the physical structure established in genome sequencing cannot be used to infer functional relationships.
The article’s goal is to establish a framework in which researchers can work to describe the genetic basis of all the moving parts needed to produce the plant’s specific product. By doing so, researchers will be able to, as completely as possible, recreate the synthetic process within another organism. To do that though, researchers must understand how each enzyme is produced, how it interacts with the substance in question, and how it functions best. Next generation sequencing allows for a more complete description of the cellular mechanics which underlie creation, and at an unprecedented speed and cost. The combination of these two fields promises the possibility of highly accessible and cost-effective drugs on a grand scale. Where time, money, and resources once limited both production and research, we could soon have quick and affordable ways to mass produce powerful anticancer drugs or antibiotics, driving down costs and driving up general public health. Or we might end up with a lot of cheap cologne. Which just sounds awful.