Dark biodiversity

Back to the future

An estimated 1 trillion microbial species populate planet Earth. Recent evidence suggests that only 0.1% of them have been identified and even fewer have been cultured, arguing that we are far from having exploited the full extent of natural metabolic diversity [1]. Today, new techniques in synthetic biology and cultivation strategies are opening access to this unexplored domain of life. DEINOVE has stepped onto this territory to extract and develop new antimicrobials against super-bugs.

As scientists progress in their exploration of microorganisms (bacteria, viruses, unicellular algae, protozoa, amoebae, fungi ...), they repeatedly revisit their predictions on the number of species present on Earth, as these always seem to fall too short. The vast majority of microorganisms – now referred to as microbial dark matter, in reference to the mysterious dark matter of the universe – have indeed remained overlooked for decades due to their low abundance, their low detection rates and the difficulty in cultivating and isolating them in a laboratory setting. But technology has changed the game. Metagenomics (the intersection of environmental microbiology, data science and next-generation sequencing) have revealed the incredible biodiversity of microbial ecosystems; it now makes it possible to capture all the genetic information present within any given sample and detect even the most underrepresented organisms. New cultivation techniques have also made it possible to tame species that were once considered uncultivatable.

A new field of life with an almost unlimited metabolic potential

But diversity in the term “biodiversity” doesn’t only refer to the very large number of living organisms available. It also refers to the wide panel of possibilities that each species, each strain, has to offer given its very own metabolism. Microorganisms perform a series of processes within what is known as “primary metabolism” that produce the molecules that are essential for survival (for example proteins, DNA or polysaccharides that are involved in fundamental functions). These are very similar across all living species and seldom show much diversity. But other processes occur within what is termed “secondary metabolism” to produce molecules that are not directly involved in growth, development or reproduction of organisms but give them a number of key competitive advantages: defense against other microorganisms, adaptability to the environment, even the most hostile ones (desert, hot spring, seabed, polluted water), etc. Secondary metabolites are small molecules produced for example in response to nutrient limitation, environmental stress or defense mechanisms. Some are common to a group of species, others are limited to a single species, others can even only appear in a single strain under very specific growth conditions. Because they are not essential for survival, they are only mildly subject to selective pressure and therefore can evolve freely resulting in a very large diversity of molecules but also highly complex compounds. 

Almost a century after the discovery of the first antibiotic in Penicillium notatum [2], the 0.1% of biodiversity that has been exploited seems to have reached its limits. But microbial dark matter today holds many promises, and DEINOVE is one of the first companies in the world to exploit this new territory and its almost unlimited metabolic potential.

 

[1] Kenneth J. Locey and Jay T. Lennon, Scaling laws predict global microbial diversity, PNAS May 24, 2016 113 (21) 5970-5975

[2] In 1945, Alexander Fleming, Howard Walter Florey and Ernst Boris Chain have shared the Nobel Prize for the discovery of penicillin.