5-Aminolevulinic acid (5-ALA) plays a pivotal role in the biosynthesis of heme and chlorophyll and has garnered great attention for its agricultural applications. This study explores the multifaceted construction of 5-ALA microbial cell factories. Evolutionary analysis-guided screening identified a novel 5-ALA synthase from as the best synthase. An sRNA library facilitated global gene screening that demonstrated that and repression enhanced 5-ALA production by 74.3% and 102%, respectively. Subsequently, efflux of 5-ALA by the transporter Gdx increased 5-ALA biosynthesis by 25.7%. To mitigate oxidative toxicity, DNA-binding proteins from starved cells were employed, enhancing cell density and 5-ALA titer by 21.1 and 4.1%, respectively. Combining these strategies resulted in an strain that produced 5-ALA to 1.51 g·L in shake flask experiments and 6.19 g·L through fed-batch fermentation. This study broadens the repertoire of available 5-ALA synthases and transporters and provides a new platform for optimizing 5-ALA bioproduction.
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http://dx.doi.org/10.1021/acs.jafc.4c00903 | DOI Listing |
Neurochem Int
December 2024
Department of Neurosurgery, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy. Electronic address:
In glioblastoma, glioma-associated microglia/macrophages (GAMs) represent the major population of tumor infiltrating cells, with up to one half of the cells of the tumor mass. Recent studies have shown that microglia are involved in the maintenance of immunological homeostasis and protection against autoimmunity. However, despite the growing body of evidence on the topic, many aspects are yet to be clarified.
View Article and Find Full Text PDFCureus
November 2024
Dermatology, University of California, San Diego, USA.
Papulopustular rosacea is an inflammatory subtype of rosacea that can significantly impair patients' quality of life. Available treatment options range from anti-inflammatory topical and oral medications to laser and light therapies. Photodynamic therapy with aminolevulinic acid (ALA-PDT) has emerged as a more recent treatment option for papulopustular rosacea.
View Article and Find Full Text PDFJ Clin Monit Comput
December 2024
Department of Critical Care, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Mitochondrial oxygen tension (MitoPO2) is a promising novel non-invasive bedside marker of circulatory shock and is associated with organ failure. The measurement of mitoPO2 requires the topical application of 5-aminolevulinc acid (ALA) to induce sufficient concentrations of the fluorescent protein protoporphyrin-IX within (epi)dermal cells. Currently, its clinical potential in guiding resuscitation therapies is limited by the long induction time prior to obtaining a reliable measurement signal.
View Article and Find Full Text PDFImmunol Med
December 2024
Department of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Chronic Fatigue Syndrome (CFS) is a complex disorder characterized by prolonged, unexplained fatigue and challenging diagnosis. We report the case of a 35-year-old Japanese woman with CFS who had experienced chronic fatigue since the age of 11 years. Despite treatment with modafinil, methylphenidate, levocarnitine, and ubiquinone, the symptoms persisted.
View Article and Find Full Text PDFSheng Wu Gong Cheng Xue Bao
December 2024
School of Public Health, Shandong Second Medical University, Weifang 261053, Shandong, China.
The probiotic strain Nissle 1917 (EcN) with high biocompatibility and susceptibility to genetic modification is often applied in bacterial therapies for cancer. However, most studies have used plasmids as vectors to construct engineering strains from EcN. Plasmid-based expression systems suffer from genetic instability, and they need antibiotic selective pressure to maintain high copy number.
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