Lozano  Terol, Gema

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Lozano Terol, Gema

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Lozano Terol, Gema

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Universidad de Murcia. Departamento de Bioquímica y Biología Molecular"B" e Inmunología

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Open Access
Dynamic Lysine Acetylation Disrupts Isocitrate Lyase Function and Enables Metabolic Optimisation
(Wiley, 2026-03-30) Martínez Vivancos, Adrián; Gomariz-Turpin, Beatriz; Ortega Retuerta, Álvaro; Lozano Terol, Gema; Sola Martínez, Rosa Alba; Gallego Jara, Julia; Diego Puente, Teresa de; Bioquímica y Biología Molecular B e Inmunología
Proteomic studies have suggested that Escherichia coli isocitrate lyase (ICL) undergoes multiple acetylation events, partially inhibiting its activity. However, the molecular basis of this regulation and the contribution of individual lysine residues had not been defined. This study demonstrates that acetylation of ICL in E. coli is acetyl-phosphate–dependent and reversible by the CobB deacetylase, establishing a key post-translational regulatory mechanism within the glyoxylate shunt. Site-specific acetylation at K13 and K308 inhibits ICL activity by destabilising the tetrameric assembly and rendering the protein more prone to degradation, whereas lysine-to-arginine substitutions at these positions alleviate this inhibition, enhancing carbon flux distribution, metabolic flexibility and biomass yield without the burden of plasmid-based overexpression. Leveraging this regulatory insight, a KR mutant bearing lysine-to-arginine substitutions at residues 13 and 308, engineered directly into the chromosomal aceA gene, maintained wild-type growth rates while reducing acetate overflow and improving metabolic balance during glucose depletion and acetate assimilation, leading to a 61% increase in lycopene production. These findings highlight regulatory-based metabolic engineering as a powerful strategy to optimise bioproduction and pave the way for extending this approach to other central metabolic enzymes to develop robust microbial cell factories for the sustainable synthesis of biofuels, biochemicals and high-value compounds.
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Engineering of microbial cell factories for production of plant-based natural products
(Elsevier, 2021) Gallego Jara, Julia; Lozano Terol, Gema; Sola Martínez, Rosa Alba; Cánovas Díaz, Manuel; Diego Puente, Teresa de; Bioquímica y Biología Molecular B e Inmunología; Facultades de la UMU::Facultad de Medicina
Biotechnology has become a promising alternative to produce highly valuable products. Production using microorganisms competes with chemical synthesis and extraction from natural sources, leading to cheaper and more sustainable production. To produce natural plant products using microorganisms, the development of molecular biology techniques that allow us to genetically and metabolically modify host microorganisms is essential. Thus many biotechnological processes have been developed to obtain terpenes, alkaloids, or polyphenols with interesting applications in the pharmaceutical, food, or cosmetic industries. The increase in our knowledge regarding the metabolism of host organisms, together with the continuous development of genetic and metabolic engineering techniques, will allow, in the coming years, biotechnology to be positioned as the main way to obtain high-value plant natural products.
Open Access
Relationship between lung function and exhaled volatile organic compounds in healthy infants
(Wiley-Blackwell, 2022-01-29) Sola‐Martínez, Rosa A.; Sánchez-Solís de Querol, Manuel; Lozano Terol, Gema; Gallego Jara, Julia; García-Marcos Álvarez, Luis Vicente; Cánovas Díaz, Manuel; Diego Puente, Teresa de; NELA Study Group; Cirugía, Pediatría y Obstetricia y Ginecología; Facultad de Medicina
Objective: The aim of this study is to assess, for the first time, the relationship between the volatilome and lung function in healthy infants, which may be of help for the early detection of certain respiratory diseases. Lung function tests are crucial in chronic respiratory diseases diagnosis. Moreover, volatile organic compounds (VOCs) analysis in exhaled breath is a noninvasive technique that enables the monitorization of oxidative stress, typical of some forms of airway inflammation. Methods: Lung function was studied in 50 healthy infants of 3–8 months of age and the following parameters were obtained: forced vital capacity (FVC), forced ex piratory volume at 0.5 s (FEV0.5), forced expiratory flow at 75% of FVC (FEF75), forced expiratory flow at 25%–75% of FVC (FEF25–75), and FEV0.5/FVC. Lung function was measured according to the raised volume rapid thoracoabdominal compression technique. In addition, a targeted analysis of six endogenous VOCs (acetone, isoprene, decane, undecane, tetradecane, and pentadecane) in the exhaled breath of the children was carried out by means of thermal desorption coupled gas chromatography‐single quadrupole mass spectrometry system. Results: A negatively significant relationship has been observed between levels of acetone, tetradecane, and pentadecane in exhaled breath and several of the lung function parameters. Levels of acetone (feature m/z = 58) were significantly nega tively associated with FVC and FVE0.5, levels of tetradecane (feature m/z = 71) with FEV0.5, and levels of pentadecane (feature m/z = 71) with FEV0.5 and FEF25–75. Conclusion: The findings of this study highlight a significant association between VOCs related to oxidative stress and lung function in healthy infants.
Open Access
Impact of environmental exposures on exhaled breath and lung function: NELA Birth Cohort
(ERS publications, 2025) Sola-Martínez, Rosa A.; Jiménez Guerrero, Pedro; Sánchez-Solís de Querol, Manuel; Lozano Terol, Gema; Gallego Jara, Julia; Martínez Vivancos, Adrián; Morales Bartolomé, Eva; García-Marcos Álvarez, Luis Vicente; Diego Puente, Teresa de; NELA Study Group; Cirugía, Pediatría y Obstetricia y Ginecología; Facultad de Medicina
Introduction: Exposure to environmental factors (i.e. air pollution and second-hand tobacco smoke) have been associated with impaired lung function. However, the impact of environmental factors on lung health is usually evaluated separately and not with an exposomic framework. In this regard, breath analysis could be a noninvasive tool for biomonitoring of global human environmental exposure. Methods: Data come from 337 mother-child pairs from the Nutrition in Early Childhood Asthma (NELA) birth cohort. Levels of BTEX (benzene, toluene, ethylbenzene and xylenes) in exhaled breath from mothers and children at 3 months after birth were estimated using gas hromatography-mass spectrometry. Short-term residential exposures (breath sampling day and 15 days before breath sampling) to nitrogen dioxide, particulate matter (PM2.5) and ozone were determined by chemical dispersion/transport modelling. Forced vital capacity, forced expiratory volume in 0.5 s (FEV0.5) and forced expiratory flow at 75% of FVC and at 25%-75% of FVC were measured in infants according to the raised-volume rapid thoracoabdominal compression technique. Results: The results showed significant associations between short-term exposure to external agents and levels of benzene and toluene in exhaled breath. It was observed that exhaled levels of benzene and toluene were influenced by smoking status and outdoor air pollution in mothers, and by air pollution in infants (3 months of age). No significant relationship was observed between exposure to maternal tobacco smoking and/or short-term air pollution and lung function in healthy infants. However, there was a significant relationship between FEV0.5 and exhaled toluene in children. Discussion: These findings indicated a significant relationship between environmental exposures and exhaled levels of benzene and toluene, suggesting that breath analysis could be a helpful exposure biomonitoring tool.
Open Access
Exhaled volatilome analysis as a useful tool to discriminate asthma with other coexisting atopic diseases in women of childbearing age
(Springer Nature, 2021-07-05) Sola Martínez, Rosa Alba; Lozano Terol, Gema; Gallego Jara, Julia; Morales Bartolomé, Eva; Cantero-Cano, Esther; Sánchez-Solís de Querol, Manuel; García-Marcos Álvarez, Luis Vicente; Jiménez Guerrero, Pedro; Noguera Velasco, José Antonio; Cánovas Díaz, Manuel; Diego Puente, Teresa de; NELA study group; Bioquímica y Biología Molecular B e Inmunología; Cirugía, Pediatría y Obstetricia y Ginecología
The prevalence of asthma is considerably high among women of childbearing age. Most asthmatic women also often have other atopic disorders. Therefore, the diferentiation between patients with atopic diseases without asthma and asthmatics with coexisting diseases is essential to avoid underdiagnosis of asthma and to design strategies to reduce symptom severity and improve quality of life of patients. Hence, we aimed for the frst time to conduct an analysis of volatile organic compounds in exhaled breath of women of childbearing age as a new approach to discriminate between asthmatics with other coexisting atopic diseases and non-asthmatics (with or without atopic diseases), which could be a helpful tool for more accurate asthma detection and monitoring using a noninvasive technique in the near future. In this study, exhaled air samples of 336 women (training set (n= 211) and validation set (n= 125)) were collected and analyzed by thermal desorption coupled with gas chromatography-mass spectrometry. ASCA (ANOVA (analysis of variance) simultaneous component analysis) and LASSO+LS (least absolute shrinkage and selection operator+ logistic regression) were employed for data analysis. Fifteen statistically signifcant models (p-value< 0.05 in permutation tests) that discriminated asthma with other coexisting atopic diseases in women of childbearing age were generated. Acetone, 2-ethyl-1-hexanol and a tetrahydroisoquinoline derivative were selected as discriminants of asthma with other coexisting atopic diseases. In addition, carbon disulfde, a tetrahydroisoquinoline derivative, 2-ethyl-1-hexanol and decane discriminated asthma disease among patients with other atopic disorders. Results of this study indicate that refned metabolomic analysis of exhaled breath allows asthma with other coexisting atopic diseases discrimination in women of reproductive age.