# An Alkaloid Biosynthetic Gene Bundle in Animals

## TL;DR

This paper discovers new gene clusters in marine sponges that produce bioactive alkaloids, challenging current assumptions about how such genes are organized.

## Contribution

The study introduces a novel computational method to identify noncanonical biosynthetic gene bundles in animals, revealing 36 clusters in sponges.

## Key findings

- 36 biosynthetic gene clusters were discovered in oroidin-producing sponges, with only one cluster (oro) shared across all species.
- The 'oro' cluster contains animal-specific primary metabolic genes repurposed for alkaloid biosynthesis.
- Five proteins from the oro cluster were validated in biochemical assays, confirming their role in alkaloid production.

## Abstract

Alkaloids include
some of the most impactful molecules
used in
science and medicine. While plant alkaloids are well explored, much
less is known about the diverse bioactive alkaloids from the animal
kingdom. To solve this problem, we developed a computational method
to discover genes that are bundled in chromosomal regions, enabling
agnostic discovery of noncanonical biosynthetic gene clusters (BGCs)
without prior knowledge of what enzymes might be involved. The method
was applied to marine sponges that produce oroidin and related pyrrole-imidazole
alkaloids, uncovering 36 BGCs in oroidin-producing sponges, only one
of which (oro) was found in all species. Many of
these clusters defy current BGC dogma, leading us to suggest the name
“bundles” for this phenomenon. Five oro proteins were validated in biochemical assays. oro consists of orthologs of common, animal-specific primary metabolic
genes that have been collected in one chromosomal region and repurposed
for alkaloid biosynthesis. This provides a roadmap to accelerate the
development of oroidins and the countless other unique natural products
found in the animal kingdom.