Acetate is a cost-effective and sustainable carbon source that, despite its potential, remains underutilized. This study employed biosensor-assisted adaptive laboratory evolution (ALE) to enhance itaconic acid production and acetate metabolism in Escherichia coli. The evolved E. coli W strains exhibited 65% increase in itaconic acid production and 71% increase in growth rate, and 45% increase in itaconic acid yield. A common 31-kb genomic deletion was identified in the evolved strains, with two genes, ecw_m2276 and ecw_m2277, driving the observed phenotypic changes. The evolved strains exhibited an intensified stringent response, which enhanced the acetate-utilizing pathway and resulted in over a 5,000% increase in the expression of the glyoxylate shunt, thereby boosting microbial growth. Overexpression of relA further replicated these enhanced phenotypes. Our findings highlight not only significant physiological improvements but also present a novel strategy for enhancing microbial growth and bioproduction from acetate, offering valuable insights for industrial biotechnology applications.
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http://dx.doi.org/10.1016/j.biortech.2025.132326 | DOI Listing |
Sci Transl Med
March 2025
Clinical Neuroscience Research Center, Department of Neurosurgery and Neurology, Tulane University School of Medicine, New Orleans, LA 70112, USA.
Traumatic brain injury (TBI) rapidly triggers proinflammatory activation of microglia, contributing to secondary brain damage post-TBI. Although the governing role of energy metabolism in shaping the inflammatory phenotype and function of immune cells has been increasingly recognized, the specific alterations in microglial bioenergetics post-TBI remain poorly understood. Itaconate, a metabolite produced by the enzyme aconitate decarboxylase 1 [IRG1; encoded by immune responsive gene 1 ()], is a pivotal metabolic regulator in immune cells, particularly in macrophages.
View Article and Find Full Text PDFBioprocess Biosyst Eng
March 2025
Department of Biobased Materials Science, Kyoto Institute of Technology, 1 Hashigami-cho, Matsugasaki, Sakyo-ku, Kyoto, 606-8585, Japan.
In this study, a bio-based vinylidene monomer, itaconic acid (IA), produced by a fungus Aspergillus terreus NBRC 6123 was polymerized in the culture. The inhibition of IA polymerization by the culture components was eased by extraction with 4-methyltetrahydropyran (4mTHP). The extraction with 4mTHP for 4 days under aerobic condition resulted in IA production at 67.
View Article and Find Full Text PDFPNAS Nexus
March 2025
Max-Planck Institute for Terrestrial Microbiology, Karl-von-Frisch Strasse 14, Marburg 35043, Germany.
Itaconic acid belongs to the high-value precursors for the production of biomass-based industrial compounds. It originates from the tricarboxylic acid cycle, and depending on the organism, it is produced by different biosynthetic routes. The basidiomycete fungus synthesizes itaconic acid via isomerization of -aconitic acid to -aconitic acid, and subsequent decarboxylation catalyzed by the -aconitate decarboxylase Tad1, which belongs to the aspartase/fumarase superfamily.
View Article and Find Full Text PDFFront Immunol
March 2025
Institute of Medicine and Equipment for High Altitude Region, College of High Altitude Military Medicine, Army Medical University (Third Military Medical University), Chongqing, China.
Introduction: Macrophages, which tend to aggregate in the hypoxic regions of tissues, have a significant impact on disease progression and outcome because of their plastic responsiveness to hypoxia, particularly in the early stages. Understanding macrophages'participation in hypoxia-related disorders requires demonstrating the impact of acute hypoxia on their survival, phenotype, and function.
Methods: Here we conducted a systematic evaluation of macrophage responses to hypoxia over 24 and 48 h including cell growth and activity, inflamatory response, macrophage polarization and transcriptional and metabolic changes.
Bioresour Technol
February 2025
Department of Chemical Engineering, Pohang University of Science and Technology, 77 Cheongam-Ro, Nam-Gu, Pohang, Gyeongbuk 37673, Republic of Korea; School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, 77 Cheongam-Ro, Nam-Gu, Pohang, Gyeongbuk 37673, Republic of Korea. Electronic address:
Acetate is a cost-effective and sustainable carbon source that, despite its potential, remains underutilized. This study employed biosensor-assisted adaptive laboratory evolution (ALE) to enhance itaconic acid production and acetate metabolism in Escherichia coli. The evolved E.
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