Biosynthesis of polyamine-polyphosphate granules for colitis alleviation

TL;DR

Engineered bacteria produce polyamine-polyphosphate granules that help reduce colitis by slowly releasing anti-inflammatory polyamines in the colon.

Contribution

A novel two-step cultivation method using engineered Citrobacter freundii to biosynthesize polyamine-polyphosphate granules for colitis treatment.

Findings

CPP produced high levels of spermidine and spermine under two-step cultivation.

PPGs enable slow release of polyamines and increase colonic polyamine levels.

Oral PPGs reduced inflammation and restored gut microbiota in a colitis model.

Abstract

Natural polyamines, such as spermidine and spermine, exert strong anti-inflammatory effects, but their therapeutic benefits are limited by rapid absorption in the small intestine, resulting in low colonic availability. In this study, engineered Citrobacter freundii overexpressing ppk1 (CPP) could significantly enhance both intracellular polyamine synthesis and polyphosphates (PolyP) accumulation. Under a two-step cultivation process, the engineered strain produced substantial amounts of polyamines, including spermidine (145.14 ± 5.11 mg/g) and spermine (175.31 ± 4.2 mg/g). CPP responds to environmental stress by importing large amounts of phosphate for PolyP synthesis. This process further promotes polyamine production, which binds to PolyP to neutralize intracellular charge. The resulting polyamine-polyphosphate granules (PPGs) enhance both binding stability and slow-release properties in vivo. Notably, the oral administration of PPGs increased colonic polyamine levels, alleviated DSS-induced colitis, reduced inflammatory cytokines, and restored gut microbiota balance. Overall, biosynthesized PPGs represent a highly promising material for mitigating colitis.

•Engineered C. freundii accumulates abundant polyamines and PolyP under two-step cultivation•Phosphate uptake drives intracellular assembly of polyamines and PolyP into PPGs•PolyP in PPGs enables the slow release of polyamines and increases colonic polyamine levels•Oral PPGs alleviate colitis by restoring immune function and gut microbiota homeostasis

Engineered C. freundii accumulates abundant polyamines and PolyP under two-step cultivation

Phosphate uptake drives intracellular assembly of polyamines and PolyP into PPGs

PolyP in PPGs enables the slow release of polyamines and increases colonic polyamine levels

Oral PPGs alleviate colitis by restoring immune function and gut microbiota homeostasis

Biosynthesis; Biological sciences; Biomaterials

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