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Biosynthesis of polyamine–polyphosphate granules for colitis alleviation

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, 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.

INSTRUMENT(S): Liquid Chromatography MS - positive - reverse-phase

PROVIDER: MTBLS13621 | MetaboLights | 2026-01-07

REPOSITORIES: MetaboLights

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			Action	DRS
	a_MTBLS13621_LC-MS_positive_reverse-phase_metabolite_profiling.txt	Txt
	i_Investigation.txt	Txt
	m_MTBLS13621_LC-MS_positive_reverse-phase_metabolite_profiling_v2_maf .tsv	Tabular
	m_MTBLS13621_LC-MS_positive_reverse-phase_metabolite_profiling_v2_maf.tsv	Tabular
	s_MTBLS13621.txt	Txt

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Project description:Polyamines (putrescine, spermidine, and spermine) are major organic polycations essential for a wide spectrum of cellular processes. The cells require mechanisms to maintain homeostasis of intracellular polyamines to prevent otherwise severe adverse effects. We performed a detailed transcriptome profile analysis of P. aeruginosa in response to agmatine and putrescine with an emphasis in polyamine catabolism. Agmatine serves as precursor compound for putrescine (and hence spermidine and spermine), which was proposed to convert into GABA and succinate before entering the TCA cycle in support of cell growth as the sole source of carbon and nitrogen. Two acetylpolyamine amidohydrolases, AphA and AphB, were identified to be involved in the conversion of agmatine into putrescine. Enzymatic products of AphA were confirmed by mass spectrometry analysis. Interestingly, the alanine-pyruvate cycle was shown indispensable for polyamine utilization. The newly identified dadRAX locus, encoding the regulator, alanine transaminase and racemase respectively, coupled with SpuC, the major putrescine-pyruvate transaminase, were key components to maintain alanine homeostasis. Corresponding mutant strains were severely hampered in polyamine utilization. On the other hand, the alternative gamma-glutamylation pathway for the conversion of putrescine into GABA was also discussed. Subsequently, GabD, GabT and PA5313 were identified for GABA utilization. Growth defect of PA5313 gabT double mutant in GABA suggested the importance of these two transaminases. The succinic-semialdehyde dehydrogenase activity of GabD and its induction by GABA was also demonstrated in vitro. Polyamine utilization in general was proven independent of the PhoPQ two-component system even the expression of which was induced by polyamines. Multiple potent catabolic pathways as depicted in this study could serve pivotal roles in control of intracellular polyamine levels. Keywords: Metabolism, polyamines, agmatine, putrescine, glutamate, phoPQ.

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Biosynthesis of polyamine–polyphosphate granules for colitis alleviation

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