# Branched-chain polyamines: evolutionary adaptation and biotechnological potential

## TL;DR

Branched-chain polyamines help thermophilic organisms survive extreme heat and protect DNA, with potential uses in biotechnology and diagnostics.

## Contribution

This review highlights the unique structure and function of BCPAs and their biotechnological potential for DNA amplification and diagnostics.

## Key findings

- BCPAs bind DNA more strongly than linear polyamines and induce structural transitions that protect DNA from damage.
- Loss of BCPA biosynthesis in Thermococcus kodakarensis impairs high-temperature growth and stress responses.
- Immobilized BCPAs enable sensitive DNA capture and amplification from dilute samples.

## Abstract

Branched-chain polyamines (BCPAs), exemplified by N⁴-bis(aminopropyl)spermidine, are distinctive polycations that occur predominantly in thermophilic bacteria and euryarchaeal archaea. Their dedicated aminopropyltransferase, BpsA (EC 2.5.1.128), extends spermidine into branched architectures via sequential decarboxylated S-adenosylmethionine (dcSAM)-dependent reactions. Accumulated evidence demonstrates that BCPAs engage nucleic acids with substantially higher affinity than linear polyamines such as spermidine, and they uniquely induce strong DNA compaction accompanied by B→A→C structural transitions. These interactions greatly enhance the resistance of DNA to thermal, chemical, and physical damage. Genetic and physiological analyses in Thermococcus kodakarensis further show that loss of BCPA biosynthesis compromises growth at very high temperatures, disrupts temperature- and membrane-associated stress responses, and alters transcriptional and translational regulation; intriguingly, the linear tetraamine thermospermine can partially substitute for BCPA in several of these functions. Beyond cellular physiology, immobilized BCPAs enable sensitive nucleic-acid capture and direct PCR and isothermal DNA amplification from highly dilute solutions, demonstrating their potential utility in molecular diagnostics and environmental DNA workflows. This review synthesizes current knowledge of BCPA distribution, biosynthesis, structure–function relationships, cellular roles, and emerging biotechnological applications, and highlights key open questions in the field.