Paleolithic molecules were resurrected from ancient dental plaques

In a groundbreaking study, scientists reconstructed ancient bacterial genomes from human and Neanderthal dental plaques, discovering previously unknown metabolites called paleofurans, providing valuable insights into early hominin health and nutrition.

Reconstruction of bacterial genomes recovered from calcified plaque of human and Neanderthal remains has provided new insights into previously undescribed Pleistocene bacterial metabolism, researchers report. This approach expands the ability of researchers to study microbial natural products, which are otherwise mostly limited to studying living bacteria.

Bioactive small molecules produced by microorganisms, often called natural products, are an important source of various functional compounds for industry and medicine, including many antibiotics. Characterization of natural products encoded in biosynthetic gene clusters (BGCs) produced by microbes of the ancient microbiota will provide valuable insight into previously unknown metabolites and their role in the nutrition and health of early hominins.

Using ancient DNA, biochemists have succeeded in producing molecules—paleofurans (shown here in powder form). Credit: Anna Schroll/Leibniz-HKI

Although recent advances in paleogenomics have illuminated past genetic diversity in humans, the functions and biosynthetic capabilities of this rapidly evolving paleome remain elusive.

Martin Clapper and colleagues searched for biosynthetic gene clusters in metagenomic datasets extracted from calcified dental plaque or dental calculus from ancient human and Neanderthal remains spanning the past 100,000 years.

They reconstructed 459 bacterial metagenome-assembled genomes (MAGs). Some MAGs are more than 90,000 years older than previously reconstructed MAGs. Within this model, Clapper and many others. Discovered previously undescribed Pleistocene bacteria[{” attribute=””>species within the genus Chlorobium, which contained a BGC shared by seven Middle and Upper Paleolithic individuals.

Microbes are Nature’s greatest chemists, and by studying the genomes of ancient bacteria, it may be possible to discover new uses for very old molecules. Credit: Werner Siemens Foundation, Felix Wey

Using heterologous expression techniques to reconstruct the biosynthetic action of these ancient BGCs, the authors found that they produced previously unreported metabolites, namely 5-alkylfuran-3-carboxylic acid products that the authors dub paleofurans.

According to the authors, the findings demonstrate the paleobiotechnological approach’s potential in future natural product exploration in ancient metagenomes.

“By merging metagenomics, genome mining, gene synthesis, and metabolic analyses with the field of [ancient DNA] Research, we chart the path to discovery of ancient natural materials to gain evolutionary insights into their formation and origin and inform their potential future applications,” Clapper writes. and many others.

For more on this research, see Biochemists „Recover” Stone Age Molecules from Ancient DNA.

Reference: Martin Clapper, Alexander Huebner, Anon Ibrahim, Ina Wasmuth, Maxim Bori, Weid G. Hansch, Shuiping Zhang, Walid K. Sumal, Harikumar, Al-Jammal, “Natural products from reconstructed bacterial genomes of the Middle and Upper Paleolithic” James A. Fellows Yates, Jasmine Frankenberg, Irina M. Velsko, Somak Chaudhary, Rosa Herbst, Evgeny V. Bradovanov, Hans-Martin Dahce, Therese Horch, Christian Hertweg, Manuel Ramon Gonzalez Morales, Lawrence Vernersive Cui, and Pierre Stallforth, 4 May 2023, Science.
DOI: 10.1126/science.adf5300