2026/06/08 by Fatima El Arnouki Belhaji, Dries De Ruysscher, Giel Vanreppelen +14 · 1 voice
Medicine · Chemistry · #Microbial Natural Products and Biosynthesis #Carbohydrate Chemistry and Synthesis #Synthetic Organic Chemistry Methods
paper · doi:10.1021/jacsau.6c00386
High Resolution Image Download MS PowerPoint Slide Polyunsaturated fatty acid (PUFA) synthase enzymes are best known for their role in membrane lipid biosynthesis in marine psychrophilic bacteria but have also evolved to assemble specialized lipid-containing metabolites with unique biological functions. Here, we illuminate their broader biosynthetic potential by charting the unexplored landscape of hybrid peptide-polyketide-specialized lipid biosynthesis in bacteria. Using a targeted genome mining strategy, we identified more than 60 biosynthetic gene clusters that encode PUFA synthase-like, polyketide synthase (PKS), and nonribosomal peptide synthetase (NRPS) enzymes across diverse bacterial lineages. Comparative analysis revealed extensive diversification of these triple hybrid pathways through gene fusion, domain reshuffling, and enzyme recruitment. We further expand the known repertoire of peptide-polyketide-specialized lipid hybrids by identifying the chitinimines, a new family of amphiphilic metabolites produced by Chitinimonas koreensis featuring a C22 polyunsaturated lipid conjugated to a cyclic peptide-polyketide and a pyruvate-derived cyclic acetal moiety. The chitinimines exhibit surfactant properties, as well as moderate activity against Gram-positive bacteria, and contribute to a growth-promoting effect on Salmonella serovars. Together, these findings demonstrate that PUFA synthase-like systems are far more versatile than previously appreciated, playing a key role in combinatorial biosynthetic innovation and serving as a rich, untapped source of chemically and functionally diverse specialized lipids.