Marine sponges have been central to most research that reef scientists refer to as the development of “marine drugs.” The chemical makeup of their life processes is unusual, diverse, and well-studied.
Other visible reef organisms rank lower. For example, reef-building corals barely made the cut. During a study that cataloged the genomes of hundreds of microorganisms inhabiting these places, it became clear why this was a mistake.
Samples were collected during a Pacific expedition that concluded in 2018. Researchers aboard the schooner Tara retrieved over 800 coral fragments from reefs around some 30 islands.
Shinichi Sunagawa, a microbial ecologist at ETH Zurich, led the team that assembled these fragments into microbial genomes. The study discovered 645 species of microorganisms, bacteria, and ancient single-celled organisms called archaea. All of them lived on or within three groups of reef-building corals. The findings were published in the journal Nature.
More than 99 percent of these species had never been recorded in any genome database. Sunagawa explained that they were virtually unknown to science.
The researchers checked if these microbes could have entered the water from open seas. It turned out they had not. When the team compared coral samples with seawater taken at various distances, it was found that the coral microbiome was virtually absent more than a few feet away from its host.
Even on the same reef, different corals hosted different communities of microorganisms. Across the three coral groups studied, 95 percent of microorganism species were found only on a single type of host coral.
This was compared to how human skin and gut microbes attach to specific body parts. Such host-specific localization was described in a recent review.
These microbes are not idle. To protect themselves from pathogens, predators, and competitors in a crowded ecosystem, they appear to produce chemicals. Many of these are the very small molecules that pharmaceutical companies spend fortunes inventing.
The team scanned each genome for genetic instructions that marine microbes use to synthesize these chemicals. Reef microbes contained more such recipes per species than a group of researchers found in an earlier open-ocean study in the open ocean. Roughly 64 percent of these genetic blueprints had never been described before.
These are not just modifications of compounds already on chemists’ shelves. They are recipes for chemical reactions not yet created. Fire corals, named for the stinging sensation they inflict on swimmers who brush against them, were not expected to dominate this analysis.
Traditionally, much reef research has focused on stony corals, the primary builders of coral reefs. It turns out, however, that fire corals possess the richest microbiomes of all three groups.
Within each species, the microbes contained nearly twice as many gene clusters for making chemicals as did the microbes of soft corals, the focus of earlier research.
Decoding genetic instructions for chemical reactions is not the same as proving they work. The team selected a few promising targets. Then they ran them through the entire process, turning genetic instructions into a functional enzyme, and then into a testable chemical.
One target stood out. An understudied bacterium from a coral’s microbiome contained instructions for making a small protein adorned with the circular chemical groups found in many drugs currently on the market.
When researchers recreated the assembly machinery in a lab strain of bacteria, they were able to produce the modified protein in a controlled setting. The drug blocked a human neutrophil elastase, an enzyme that causes tissue damage in inflammatory diseases, at concentrations low enough to interest drug developers.
The team also showed that the assembly enzyme worked with truncated versions of the protein and proteins engineered for different tasks. It is this kind of flexibility that a biotech lab looks for in a starting tool.
Natural compounds have been found in marine organisms for decades. However, systematic studies within reef-building corals had been virtually nonexistent before this work.
Three coral genera were included in this analysis. Hundreds more exist.
Sponges, mollusks, and algae host a vast array of diverse microbial communities, virtually none of which have been studied at this resolution. Each could be a source of novel enzymes, antibiotics, or medicines, and each is shrinking as warming waters threaten their environments.
Arguments for protecting reefs have long relied on tourism, fisheries, and coastal protection from storm waves. Their molecular value has been secondary. Medicines have occasionally been isolated from reef organisms, but a complete inventory of the microorganisms they contain did not exist.
The current inventory covers three coral types in one oceanic basin. Reef microbiomes hold more genes coding for chemicals per organism than those in the surrounding sea.
Most of them remain unexplored, but one expedition discovered a working enzyme of interest to the pharmaceutical industry.
“Molecular exploration of coral reefs offers enormous opportunities for biotechnological and medical applications,” said Jörn Piel of the Swiss Federal Institute of Technology Zurich.
The primary challenge is time. Reefs are disappearing faster than the chemical makeup of their waters can be measured, and much of what is lost will never be studied again.
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