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“Digging” for biosynthetic diversity reveals untapped nature’s potential

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Posted February 23, 2015

As consumers, we tend to think of drug companies as the ultimate source of all medicines, when in fact, quite the opposite is true. Our everyday painkillers, antibiotics, cholesterol-lowering drugs and even certain cancer therapies actually come from nature – and what we currently make use is just a fraction of the entire nature’s biosynthetic potential.

Citizen science project "Drugs From Dirt" looked at soil samples from distinct geographical and ecological locations to reveal biosynthetic diversity of soil bacteria. Photograph by Abrahim El Gamal.

Citizen science project “Drugs From Dirt” looked at soil samples from distinct geographical and ecological locations to reveal biosynthetic diversity of soil bacteria. Photograph by Abrahim El Gamal.

Bacteria, for example, are used to producing compounds that fend off rival species, help compete for food sources and create an otherwise favorable environment for living. These molecules are not directly used by the bacteria themselves and are thus labeled as “natural products”. One of the most famous natural products is penicillin, which revealed itself by preventing fungal growth in a historic (and accidental) experiment that led to the antibiotic era. Since then, numerous other bacteria-derived natural products have been employed to human use, including cytotoxic compounds used to fight cancer.

The most straightforward way to make use natural compounds is to isolate a particular bacterium, grow it in the lab and extract what is it we need from it – a new antibiotic or something with completely novel medical properties. Having in mind the overall diversity of microbes on Earth (some scientists estimate there are up to 10 million or more bacterial species out there, and this is just a guess), it should be relatively easy, right?

Wrong! Isolation of natural products is much easier said than done, since most bacteria are actually impossible or nearly impossible to grow in the lab, which hides them and all of their biosynthetic potential from us completely.

Fortunately, metagenomic methods are now allowing researchers to extract and sequence bacterial genomes directly, without the culturing step. This way, the scope of the actual biodiversity can be glimpsed in crude environmental samples.

A citizen science project “Drugs From Dirt” has recently set out to explore nature’s drug-producing abilities by sequencing bacterial genomes from soil. Some of their findings were published last month on eLife.

By analyzing a hundred distinct soil samples from all over the world, a joint team of researchers from the United States, Brazil, South Africa and China were able to witness a vast biodiversity of natural producers – a glimpse of the bacterial “biosynthetic dark matter”.

Soil samples were collected from five different continents and a range of distinct biomes, including Atlantic forest, saline or cerrado environments, desert topsoils and hot springs sediments. Image from eLife 2015;4:e06453.

Soil samples were collected from five different continents and a range of distinct biomes, including Atlantic forest, saline or cerrado environments, desert topsoils and hot springs sediments. Image from eLife 2015;4:e06453.

Interestingly, bioinformatic analysis of genomic data revealed great differences between biosynthetic genes in different biomes, i.e. locations where ecological conditions are distinct, even when the sites were close geographically. For example, Brazilian soil samples from Atlantic rainforest, cerrado (tropical savanna) and aquatic sites collected only a few miles apart were only distantly related. It comes to no surprise then that samples collected from different biomes as well as geographical locations contribute to massive biosynthetic diversity.

Natural products clearly have significant ecological roles, since genes encoding these properties are so versatile across different niches. However, the function of most of these compounds remains unknown, even though some soil bacteria are known to dedicate a large part (up to 10%) of their genomes to this cause. Nevertheless, we are more than likely to discover more medically useful compounds within this pool.

“Based on the historical success of natural products as therapeutics, microbial ‘biosynthetic dark matter’ is likely to hold enormous biomedical potential”, the researchers concluded.

The trick now is to harvest and put these natural molecules to work, for which biosynthetic “hot-spots” (particularly rich biomes) discovered by “Drugs From Dirt” are definitely a good place to start.

Written by Eglė Marija Ramanauskaitė

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