Research group of Microbial Metabolic Engineering and System Biology, led by Prof. Chen YANG from Center for Excellence in Molecular Plant Sciences of the Chinese Academy of Sciences (CAS), has discovered a novel bacterial spermidine biosynthetic pathway, i.e., CAPA pathway, widely distributed in diverse bacteria including Proteobacteria, Firmicutes and Bacteroidetes. The research article entitled “A bacterial spermidine biosynthetic pathway via carboxyaminopropylagmatine” was published online in Science Advances on October 25^th, 2023.

 

Polyamines are small organic polycations containing two or more amines. They are found in almost all cells of bacteria, archaea, and eukaryotes and play important roles in a variety of cellular processes, including gene regulation, cell proliferation and differentiation, and adaptation to various stresses. Spermidine, the most ubiquitous triamine in the three domains of life, is considered almost certainly present in the last universal common ancestor of life (LUCA). There are two principal pathways for the synthesis of spermidine, which involve direct or indirect aminopropylation of diamine putrescine.

 

In this study, the authors identified a spermidine biosynthetic pathway via a previously unknown metabolite, carboxyaminopropylagmatine (CAPA), in a model cyanobacterium Synechocystis sp. PCC 6803 through an approach combining stable isotope tracers, metabolomics, and genetic and biochemical characterization. The CAPA pathway starts with reductive condensation of agmatine and l-aspartate-β-semialdehyde into CAPA by a novel CAPA dehydrogenase, followed by decarboxylation of CAPA to form aminopropylagmatine (APA), and ends with conversion of APA to spermidine by an APA ureohydrolase. Thus, the pathway does not involve putrescine and depends on l-aspartate-β-semialdehyde as the aminopropyl group donor. Genomic, biochemical, and metagenomic analyses showed that the CAPA-pathway genes are widespread in 15 di？erent phyla of bacteria distributed in marine, freshwater, animal digestive system, and other ecosystems.