Search bioRxivSearch

bioRxiv · 10.1101/2020.01.22.916338

Accumulation of ammonium owing to the metabolic imbalance of carbon and nitrogen might inhibit the central metabolism in Methylomonas sp. ZR1

Abstract

The metabolic intermediates of nitrogen source have been proved to have multiple functions on the metabolism of mehthanotrophs. In this study, accumulation and assimilation mechanism of the nitrate metabolic intermediate ammonium in the fast growing Methylomonas sp. ZR1 was analyzed. Although, nitrate salt was the best nitrogen source supporting the growth of ZR1, its metabolic intermediate ammonium would accumulate and inhibit ZR1. Kinetic studies indicated that accumulation of NH4+ was deduced from the imbalance of nitrogen and carbon metabolism. Compensation of carbon skeleton -keto-glutaramate could effectively relieve the inhibition of NH4+ to ZR1, which further approved the assumption. qPCR analysis indicated a third ammonium assimilation pathway Glycine synthesis system may function in ZR1 under high ammonium tension. In the presence of ammonium, ZR1 might employ two strategies to relieve the ammonium stress, one was assimilating the excess ammonium, and another one was cutting off the nitrogen reduction reactions. Investigation of the nitrogen metabolism and its influence to the carbon metabolism is meaningful to systematically understand and control the C1 feedstock bioconversion process in methanotrophs. ImportanceThe nitrogen metabolism in methanotrophs has long been concerned. However, there are lots of research problems yet to be solved. In this study, the accumulation and assimilation mechanism of the nitrogen metabolic intermediate ammonium in the fast growing Methylomonas sp. ZR1 was analyzed. Owing to the imbalance metabolism of carbon and nitrogen source, ammonium would accumulate to high concentrations to inhibit cell growth. Compensation of carbon skeleton was an effective strategy to relieve the inhibition of NH4+. A third ammonium assimilation pathway related genes were proved actively expressing in ZR1 when it confronted with high ammonium tension. When confronted with ammonium tension, ZR1 might employ different strategies to relieve the ammonium stress according to the edible carbon source. Revealing the endogenous ammonium accumulation mechanism and its metabolic adjustment effect on the central metabolism of methanotrophs, was meaningful to reveal the complex coordination metabolic mechanism of nitrogen and carbon in methanotrophs.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Guo, W., He, R., Zhao, Y., Li, D.. 2020-01-23. Accumulation of ammonium owing to the metabolic imbalance of carbon and nitrogen might inhibit the central metabolism in Methylomonas sp. ZR1. https://doi.org/10.1101/2020.01.22.916338

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

IBD-Derived Colonic Fibroblasts Exhibit an Osteopontin-Enriched Secretome, and Osteopontin Restrains Human Colonic Organoid Maturation

Background: Intestinal fibroblasts are extensively remodeled in inflammatory bowel disease (IBD), yet the soluble stromal signals that directly influence epithelial maturation remain incompletely understood. We examined whether fibroblasts derived from inflamed IBD colon display an osteopontin (OPN; SPP1)-enriched secretory phenotype and whether extracellular OPN directly modifies non-neoplastic human colonic epithelium. Methods: Conditioned media from 5 noninflamed-associated fibroblast (NAF) and 4 inflammatory-associated fibroblast (IAF) cultures were analyzed in the validated multi-donor cytokine-array matrix, with orthogonal SPP1 RT-qPCR validation in a complementary fibroblast cohort. Recombinant OPN was then tested in human colonic organoids from 3 donors using donor-resolved molecular and functional analyses under standard, fibroblast-conditioned, and WNT-modified culture conditions. Donor identity defined biological replication. Results: OPN showed the strongest positive rank-based separation between IAF and NAF cultures: all 4 IAF values were higher than all 5 NAF values (Cliff's delta=1.00; exact Mann-Whitney P=0.0159; median ratio=3.64; Benjamini-Hochberg q=.19). Fibroblast RT-qPCR showed approximately 10-fold higher mean SPP1 expression in IAF than NAF cultures (P<.05). In organoids, OPN consistently reduced KRT20, FABP1, CA2, and MUC2 from Day 5 to Day 9. SOX9, HES1, and NOTCH1 increased at Day 9, whereas LGR5 and ALDH provided no evidence of canonical stem-cell expansion. Organoid-area and EdU responses were modest and donor dependent. Conclusions: IBD-derived colonic fibroblasts can display an OPN-enriched secretory phenotype. In human colonic organoids, OPN is sufficient to impair epithelial maturation, whereas its effects on growth and proliferation are variable and depend on the surrounding niche.

physiology

A multiscale analysis of liver lobule fibrosis and its impact on drug propagation and metabolism - a DLA approach

Employing DLA methods, this paper explores the self-assembly of collagen fibers and resulting fibrosis at three scales up to the scale of regular lobule models. This allows a mechanistic exploration of the effects of collagen on drug transport (flow and diffusion) and metabolism. In addition, this method permits an analysis of fiber growth characteristics. First, variations of the DLA method of Parkinson et al (1994) will be used to generate multiple explicit collagen microfibril self-assembly using DLA particles in one dimension using cubic grid blocks of (4 mm)3 in a 240 x 20 x 20 grid model. The second stage will be to assess the consequences of various densities of these fibers in three dimensions on flow reductions at a higher scale. Here we utilize DLA methods in cubic grid blocks of (80 nm)3 to mimic 3D collagen self-assembly of fibrils. We then apply a pressure gradient or specified flow rates across a spatially gridded version of these models to quantify flow effects. This region represents a local zone of liver tissue affected by fibrosis. Analytic models of fibrotic effects on flow are employed for comparison. A third stage explores the implications of fibrosis in a liver lobule model using multiple grid blocks of size 3200 mm to represent the lobule tissue. Here, a continuum model of fiber density is employed, based on the previous two scales. The model also includes the effects of additional grid blocks representing sinusoidal flow paths found in the lobule. We contrast and quantify drug propagation and metabolism of molecular dissolved versus nanoparticle delivery vehicles in fibrotic media, achieved by upscaling explicit collagen distributions to appropriate average values.

physiology

Pulmonary pressure load shapes right ventricular molecular remodelling in dilated cardiomyopathy

Right ventricular (RV) adaptation to pulmonary hypertension determines outcome in dilated cardiomyopathy (DCM), but the molecular mechanisms of the transition to decompensation remain unclear. We analysed RV tissue from explanted hearts of patients with end-stage DCM using single-nucleus RNA sequencing (n=21), mass spectrometry and Olink Reveal proteomics (both n=44), and integrated these molecular profiles with echocardiographic and right-heart catheterisation measures to identify molecular correlates of RV dysfunction. Mean pulmonary arterial pressure was the dominant correlate of RV transcriptional remodelling, particularly in cardiomyocytes, where higher pressure was associated with contractile remodelling, autophagy, vesicle trafficking and glucose metabolism. In contrast, RV decompensation was characterised by immune activation and reduced oxidative phosphorylation exclusively at the proteomic level. Integrative multi-omics factor analysis (MOFA) further identified fibrosis as the dominant molecular program shared across transcriptomic and proteomic layers. Together, these findings indicate molecular adaptation to pressure load and tissue fibrosis during progression towards RV failure.

physiology