Bacterial natural product biosynthetic domain composition in soil correlates with changes in latitude on a continent-wide scale

Abstract

Although bacterial bioactive metabolites have been one of the most prolific sources of lead structures for the development of small-molecule therapeutics, very little is known about the environmental factors associated with changes in secondary metabolism across natural environments. Large-scale sequencing of environmental microbiomes has the potential to shed light on the richness of bacterial biosynthetic diversity hidden in the environment, how it varies from one environment to the next, and what environmental factors correlate with changes in biosynthetic diversity. In this study, the sequencing of PCR amplicons generated using primers targeting either ketosynthase domains from polyketide biosynthesis or adenylation domains from nonribosomal peptide biosynthesis was used to assess biosynthetic domain composition and richness in soils collected across the Australian continent. Using environmental variables collected at each soil site, we looked for environmental factors that correlated with either high overall domain richness or changes in the domain composition. Among the environmental variables we measured, changes in biosynthetic domain composition correlate most closely with changes in latitude and to a lesser extent changes in pH. Although it is unclear at this time the exact mix of factors that may drive the relationship between biosynthetic domain composition and latitude, from a practical perspective the identification of a latitudinal basis for differences in soil metagenome biosynthetic domain compositions should help guide future natural product discovery efforts.

Diversity of Bacterial Biosynthetic Genes in Maritime Antarctica

“…target the highly conserved ketosynthase (KS) and adenylation (AD) domains of PKS and NRPS genes, respectively. A growing number of studies have employed the PCR-based sequence tag approach to uncover PKS and NRPS gene diversity across different environmental microbiomes [7][8][9].Extreme environments, such as Antarctica, have the potential to reveal novel molecules since they are still a poorly explored source of chemical scaffolds and novel chemical diversity [10,11]. As such, metabarcoding approaches to study PKS and NRPS diversity in Antarctic ecosystems represent a simple and effective strategy to understand the biosynthetic potential of a large number of sampling sites [7].…”

“…target the highly conserved ketosynthase (KS) and adenylation (AD) domains of PKS and NRPS genes, respectively. A growing number of studies have employed the PCR-based sequence tag approach to uncover PKS and NRPS gene diversity across different environmental microbiomes [7][8][9].…”

Cyclo(tetrahydroxybutyrate) production is sufficient to distinguish between Xenorhabdus and Photorhabdus isolates in Thailand

“…A recent study in Australia examined the differences between the biosynthetic domain compositions in soil across the continent. One key finding from this was that the composition of natural product domains, specifically ketosynthase domains (from PKS) or adenylation domains (from NRPS), changed with latitude and longitude and was often grouped in accordance with the vegetation type (Lemetre et al ., ). This supports our original premise that natural product composition from the Xenorhabdus and Photorhabdus may change within the country.…”

Focused natural product elucidation by prioritizing high-throughput metabolomic studies with machine learning

“…A recent study in Australia examined the differences between the biosynthetic domain compositions in soil across the continent. One key finding from this was that the composition of natural product domains, specifically ketosynthase domains (from PKS) or adenylation domains (from NRPS), changed with latitude and longitude and was often grouped in accordance with the vegetation type 28 . This supports our original premise that natural product composition from the Xenorhabdus and Photorhabdus may change within the country.…”