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PubMed2025

Versatile sugar and valerate metabolic pathways in Paraburkholderia xenovorans LB400 enable tailored poly(3-hydroxybutyrate-co-3-hydroxyvalerate) production.

Poly(3-hydroxybutyrate) and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) polymers are accumulated by diverse prokaryotes. Their distinct monomer compositions enable their use as tailored bioplastics. The aims were to characterize the poly(3-hydroxybutyrate) and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) synthesis by Paraburkholderia xenovorans LB400 using different sugars and valerate, and to gain genome-oriented insights into polyhydroxyalkanoate production. d-Glucose, d-mannitol, d-gluconate, and d-xylose were evaluated as sole carbon sources or supplemented with valerate. Polyhydroxyalkanoates synthesized by strain LB400 were characterized through GC-MS, GC-FID, FTIR, and 1H and 13C-NMR. P. xenovorans LB400 reached 1.00-1.39 g L-1 of dry cell weight (DCW) with a P(3HB) content of 21-43% w w-1 when grown on different sugars. The addition of valerate to the sugar-grown LB400 cultures yielded a DCW of 1.79 to 2.29 g L-1 and a P(3HB-co-3HV) content of 50.0‒51.2% w w-1, with varying 3HV compositions (28‒43 mol%). The highest 3HV incorporation was observed with d-xylose and valerate. Genomic analyses of strain LB400 revealed key elements of sugar metabolism influencing growth, polymer accumulation, and monomer composition. LB400 genome encodes the PhaJ-like R-specific hydratase and FadJ epimerase, which are potentially useful for modulating copolymer composition. PHA production under bioreactor conditions was evaluated. In a bioreactor fed with d-glucose, LB400 achieved a P(3HB) concentration of 2.2 g L-1. These findings highlight the metabolic versatility of P. xenovorans LB400 in utilizing diverse sugars to produce either P(3HB) or tailor-made P(3HB-co-3HV), supporting the development of bioplastics for specific applications. KEY POINTS: • Strain LB400 produced P(3HB-co-3HV) from various sugars and valerate. • Sugar type drives LB400 PHA copolymer synthesis and composition. • Strain LB400 PHA production was scaled up to a bioreactor.

Polyesters↗

PubMed2026

Broad-spectrum biodegradation of aliphatic and aliphatic-aromatic polyesters by Papiliotrema laurentii isolated from locust frass.

Biodegradable aliphatic and aliphatic-aromatic polyesters, such as poly(butylene adipate-co-terephthalate) (PBAT), polylactic acid (PLA), polycaprolactone (PCL), polybutylene succinate (PBS), and polyhydroxyalkanoates (PHA), are increasingly used as sustainable alternatives to petrochemical plastics. However, their depolymerization outside industrial composting facilities is often incomplete. This study characterized Papiliotrema laurentii strain 62UF-13, isolated from migratory locust frass, for broad-spectrum polyester hydrolysis. Emulsion assays demonstrated hydrolytic activity across all five polymers, with PCL and PBS showing the highest clearance rates. Solid-film assays revealed substantial gravimetric mass loss of PCL, PLA, and PHA cast films, whereas a commercial PBAT-PLA mulch film in minimal medium, underwent progressive fragmentation/disintegration, as assessed by the remaining film area. Incubation with the PBAT-PLA film was accompanied by the release of adipic acid (49.60 mg/L, week 1) and terephthalic acid (maximum 21.62 mg/L, week 4), followed by a decrease to 0.26 mg/L by week 8, coinciding with the emergence of putative 3,4-dihydroxymandelic acid and a putative acetylated derivative. Scanning electron microscopy (SEM) revealed pronounced pitting and erosion, while Fourier-transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC) indicated ester-bond scission and changes in crystallinity/melting behavior. Whole-genome sequencing identified eight candidate polyesterases, including cutinases and esterases, with ≥ 60% amino acid identity to known hydrolases active on PCL, PBS, PHA, and PLA. This study is the first report of P. laurentii degrading a broad range of aliphatic and aliphatic-aromatic polyesters, including partial biotransformation of terephthalate moieties from PBAT. Integration of phenotypic assays and genomic evidence positions P. laurentii 62UF-13 as a viable biocatalyst for decentralized management of biodegradable plastic waste under mild environmental conditions.

Papiliotrema laurentii↗

PubMed2025

The functional study of novel KLHL3 missense mutations associated with pseudohypoaldosteronism type II.

BACKGROUND: Pseudohypoaldosteronism type II (PHA II) is an inherited tubulopathy, clinically defined by three hallmark features, including secondary hypertension, hyperchloremic metabolic acidosis, and persistent hyperkalemia occurring despite maintained glomerular filtration function. Herein, we aim to investigate the association of kelch like family member 3 (KLHL3) gene mutations with PHA II. METHODS: Compound heterozygous KLHL3 mutations were identified through whole-exome sequencing and Sanger validation. AlphaFold-based structural modeling, site-directed mutagenesis of Flag-tagged plasmids, and co-immunoprecipitation (Co-IP)/immunoblotting in vivo were combined to analyze mutant protein interactions and ubiquitination effects. RESULTS: A Chinese patient was identified with two previously unreported KLHL3 variants (c.131G > A [p.R44Q] and c.744 C > G [p.Y248*]), exhibiting a biochemical triad of asymptomatic hyperkalemia, mild metabolic acidosis, and borderline hypertension. Administration of thiazide diuretics effectively normalized the patient’s hyperkalemia and hypertension. A p.R44Q missense mutation predicted as variants of uncertain significance (VOUS) by American College of Medical Genetics and Genomics (ACMG) guidelines, and a p.Y248* nonsense mutation predicted as variants of likely pathogenic. Functional study revealed that the two KLHL3 mutations impair its ubiquitination of with-no-lysine kinase 1 (WNK1) and with-no-lysine kinase 4 (WNK4), and further increase phosphorylation of both SPAK (sterile20/sporulation-specific protein-1 related proline/alanine-rich kinase)/OSR1 (oxidative stress response kinase-1) and Na-Cl-cotransporter (NCC). CONCLUSIONS: Our study characterized two previously unreported KLHL3 mutations, followed by comprehensive in vitro functional analyses to elucidate their pathophysiological contributions at the molecular level.

Humans↗

PubMed2026

Biotic and abiotic degradation of PHAs: mechanisms, environments, and potential applications of degradation products.

This review seeks to compile Polyhydroxyalkanoates (PHAs) degradation studies published over the past 20 years. It highlights the effect of physical properties, such as crystallinity and molecular weight, on the decomposition rate of these molecules. Both biotic processes, mediated by bacteria, fungi, and enzymes, as well as abiotic processes, such as hydrolysis and thermal degradation, are analyzed. A repertoire of diverse microorganisms, including their metabolic pathways and enzymes for PHA breakdown, is presented. Furthermore, this review presents the decomposition of PHAs in various environments, such as soil and seawater, highlighting their potential as a sustainable alternative. Finally, the resulting degradation products are described, emphasizing their potential applications in medicine and industry. Although degradation of PHAs has been extensively studied through these years, several knowledge gaps remain undisclosed, including the degradation of diverse polyester monomers. PHAs comprise numerous monomer compositions with variable properties, which present opportunities for different applications but pose a challenge in their degradation. The reader of this review can extract useful information for both the production of PHAs and their potential applications.

Biodegradation↗

PubMed2025

Hormetic nutrient stress promotes longevity by orchestrating histone acetylation on key lipid catabolism and antioxidant defense genes.

Exposure to low levels of environmental challenges, known as hormetic stress, such as nutrient deprivation and heat shock, fosters subsequent stress resistance and promotes healthy aging in later life. However, specific mechanisms governing transcriptional reprogramming upon hormetic nutrient stress remain elusive. In this study, we identified histone H3 lysine 27 acetylation (H3K27ac) as a crucial driver of transcriptomic adaptation to hormetic fasting. Beyond its immediate function of enhancing lipid catabolism for alternative energy sources, stress-induced H3K27ac activates lifelong antioxidant defenses, thereby reducing reactive oxygen species (ROS) produced by stress-induced fatty acid oxidation and their accumulation during aging. The increase in H3K27ac, mediated by pioneer factor PHA-4/FOXA and cooperating transcription factor NHR-49/HNF4, is crucial for lifespan extension under hermetic nutrient stress in Caenorhabditis elegans. Our findings establish H3K27ac as a key transcriptional switch that bridges nutrient status with transcriptomic reprogramming, underpinning the pro-longevity effects of hormetic fasting through orchestrating lipid catabolism and antioxidative defenses.

Journal Article↗

PubMed2025

A genome-scale metabolic model for the denitrifying bacterium Thauera sp. MZ1T accurately predicts degradation of pollutants and production of polymers.

The denitrifying bacterium Thauera sp. MZ1T, a common member of microbial communities in wastewater treatment facilities, can produce different compounds from a range of carbon (C) and nitrogen (N) sources under aerobic and anaerobic conditions. In these different conditions, Thauera modifies its metabolism to produce different compounds that influence the microbial community. In particular, Thauera sp. MZ1T produces different exopolysaccharides with floc-forming properties, impacting the physical disposition of wastewater consortia and the efficiency of nutrient assimilation by the microbial community. Under N-limiting conditions, Thauera sp. MZ1T decreases its growth rate and accelerates the accumulation of polyhydroxyalkanoate-related (PHA) compounds including polyhydroxybutyrate (PHB), which plays a fundamental role as C and energy storage in this β-proteobacterium. However, the metabolic mechanisms employed by Thauera sp. MZ1T to assimilate and catabolize many of the different C and N sources under aerobic and anaerobic conditions remain unknown. Systems biology approaches such as genome-scale metabolic modeling have been successfully used to unveil complex metabolic mechanisms for various microorganisms. Here, we developed a comprehensive metabolic model (M-model) for Thauera sp. MZ1T (iThauera861), consisting of 1,744 metabolites, 2,384 reactions, and 861 genes. We validated the model experimentally using over 70 different C and N sources under both aerobic and anaerobic conditions. iThauera861 achieved a prediction accuracy of 95% for growth on various C and N sources and close to 85% for assimilation of aromatic compounds under denitrifying conditions. The M-model was subsequently deployed to determine the effects of substrates, oxygen presence, and the C:N ratio on the production of PHB and exopolysaccharides (EPS), showing the highest polymer yields are achieved with nucleotides and amino acids under aerobic conditions. This comprehensive M-model will help reveal the metabolic processes by which this ubiquitous species influences communities in wastewater treatment systems and natural environments.

Thauera↗