Martínez Vivancos, Adrián

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Martínez Vivancos, Adrián

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Martínez Vivancos, Adrián

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

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Open Access
Regulation of the pyrimidine biosynthetic pathway by lysine acetylation of E. coli OPRTase
(2022-08-22) Lozano Terol, G.; Cánovas Díaz, Manuel; Diego Puente, Teresa de; Gallego Jara, Julia; Martínez Vivancos, Adrián; Ortega Retuerta, Álvaro; Sola Martínez, Rosa Alba; Bioquímica y Biología Molecular B e Inmunología
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.
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
Impact of the Expression System on Recombinant Protein Production in Escherichia coli BL21
(Frontiers Media, 2021-06-21) Lozano Terol, Gema; Cánovas Díaz, Manuel; Diego Puente, Teresa de; Gallego Jara, Julia; Martínez Vivancos, Adrián; Sola Martínez, Rosa Alba; Bioquímica y Biología Molecular B e Inmunología
Recombinant protein production for medical, academic, or industrial applications is essential for our current life. Recombinant proteins are obtained mainly through microbial fermentation, with Escherichia coli being the host most used. In spite of that, some problems are associated with the production of recombinant proteins in E. coli, such as the formation of inclusion bodies, the metabolic burden, or the inefficient translocation/transport system of expressed proteins. Optimizing transcription of heterologous genes is essential to avoid these drawbacks and develop competitive biotechnological processes. Here, expression of YFP reporter protein is evaluated under the control of four promoters of different strength (PT7lac, Ptrc, Ptac, and PBAD) and two different replication origins (high copy number pMB10 and low copy number p15A). In addition, the study has been carried out with the E. coli BL21 wt and the ackA mutant strain growing in a rich medium with glucose or glycerol as carbon sources. Results showed that metabolic burden associated with transcription and translation of foreign genes involves a decrease in recombinant protein expression. It is necessary to find a balance between plasmid copy number and promoter strength to maximize soluble recombinant protein expression. The results obtained represent an important advance on the most suitable expression system to improve both the quantity and quality of recombinant proteins in bioproduction engineering.
Open Access
Impact of the Expression System on Recombinant Protein Production in Escherichia coli BL21
(2021-06-21) Lozano Terol, Gema; Cánovas Díaz, Manuel; Diego Puente, Teresa de; Gallego Jara, Julia; Martínez Vivancos, Adrián; Sola Martínez, Rosa Alba; Bioquímica y Biología Molecular B e Inmunología
Recombinant protein production for medical, academic, or industrial applications is essential for our current life. Recombinant proteins are obtained mainly through microbial fermentation, with Escherichia coli being the host most used. In spite of that, some problems are associated with the production of recombinant proteins in E. coli, such as the formation of inclusion bodies, the metabolic burden, or the inefficient translocation/transport system of expressed proteins. Optimizing transcription of heterologous genes is essential to avoid these drawbacks and develop competitive biotechnological processes. Here, expression of YFP reporter protein is evaluated under the control of four promoters of different strength (PT7lac, Ptrc, Ptac, and PBAD) and two different replication origins (high copy number pMB10 and low copy number p15A). In addition, the study has been carried out with the E. coli BL21 wt and the ackA mutant strain growing in a rich medium with glucose or glycerol as carbon sources. Results showed that metabolic burden associated with transcription and translation of foreign genes involves a decrease in recombinant protein expression. It is necessary to find a balance between plasmid copy number and promoter strength to maximize soluble recombinant protein expression. The results obtained represent an important advance on the most suitable expression system to improve both the quantity and quality of recombinant proteins in bioproduction engineering.
Open Access
Relative impact of three growth conditions on the Escherichia coli protein acetylome
(Cell Press, 2024-02-16) Lozano- Terol, Gema; Zenezini Chiozzi, Riccardo; Sola-Martínez, Rosa Alba; Heck, Albert J.R.; Cánovas Díaz, Manuel; Diego Puente, Teresa de; Gallego Jara, Julia; Martínez Vivancos, Adrián; Ortega Retuerta, Álvaro; Bioquímica y Biología Molecular B e Inmunología
Nε-lysine acetylation is a common posttranslational modification observed in Escherichia coli. In the present study, integrative analysis of the proteome and acetylome was performed using label-free quantitative mass spectrometry to analyze the relative influence of three factors affecting growth. The results revealed differences in the proteome, mainly owing to the type of culture medium used (defined or complex). In the acetylome, 7482 unique acetylation sites were identified. Acetylation is directly related to the abundance of proteins, and the level of acetylation in each type of culture is associated with extracellular acetate concentration. Furthermore, most acetylated lysines in the exponential phase remained in the stationary phase without dynamic turnover. Interestingly, unique acetylation sites were detected in proteins whose presence or abundance was linked to the type of culture medium. Finally, the biological function of the acetylation changes was demonstrated for three central metabolic proteins (GapA, Mdh, and AceA).