1. Structural basis for dysregulation of aminolevulinic acid synthase in human disease
Jessica L Taylor, Breann L Brown J Biol Chem. 2022 Mar;298(3):101643. doi: 10.1016/j.jbc.2022.101643. Epub 2022 Jan 28.
Heme is a critical biomolecule that is synthesized in vivo by several organisms such as plants, animals, and bacteria. Reflecting the importance of this molecule, defects in heme biosynthesis underlie several blood disorders in humans. Aminolevulinic acid synthase (ALAS) initiates heme biosynthesis in α-proteobacteria and nonplant eukaryotes. Debilitating and painful diseases such as X-linked sideroblastic anemia and X-linked protoporphyria can result from one of more than 91 genetic mutations in the human erythroid-specific enzyme ALAS2. This review will focus on recent structure-based insights into human ALAS2 function in health and how it dysfunctions in disease. We will also discuss how certain genetic mutations potentially result in disease-causing structural perturbations. Furthermore, we use thermodynamic and structural information to hypothesize how the mutations affect the human ALAS2 structure and categorize some of the unique human ALAS2 mutations that do not respond to typical treatments, that have paradoxical in vitro activity, or that are highly intolerable to changes. Finally, we will examine where future structure-based insights into the family of ALA synthases are needed to develop additional enzyme therapeutics.
2. 5-aminolevulinic acid-mediated plant adaptive responses to abiotic stress
Mohammad Saidur Rhaman, et al. Plant Cell Rep. 2021 Aug;40(8):1451-1469. doi: 10.1007/s00299-021-02690-9. Epub 2021 Apr 10.
5-aminolevulinic acid (ALA) modulates various defense systems in plants and confers abiotic stress tolerance. Enhancement of crop production is a challenge due to numerous abiotic stresses such as, salinity, drought, temperature, heavy metals, and UV. Plants often face one or more abiotic stresses in their life cycle because of the challenging growing environment which results in reduction of growth and yield. Diverse studies have been conducted to discern suitable mitigation strategies to enhance crop production by minimizing abiotic stress. Exogenous application of different plant growth regulators is a well-renowned approach to ameliorate adverse effects of abiotic stresses on crop plants. Among the numerous plant growth regulators, 5-aminolevulinic acid (ALA) is a novel plant growth regulator, also well-known to alleviate the injurious effects of abiotic stresses in plants. ALA enhances abiotic stress tolerance as well as growth and yield by regulating photosynthetic and antioxidant machineries and nutrient uptake in plants. However, the regulatory roles of ALA in plants under different stresses have not been studied and assembled systematically. Also, ALA-mediated abiotic stress tolerance mechanisms have not been fully elucidated yet. Therefore, this review discusses the role of ALA in crop growth enhancement as well as its ameliorative role in abiotic stress mitigation and also discusses the ALA-mediated abiotic stress tolerance mechanisms and its limitation and future promises for sustainable crop production.
3. Advances in 5-Aminolevulinic Acid Priming to Enhance Plant Tolerance to Abiotic Stress
Shuya Tan, Jie Cao, Xinli Xia, Zhonghai Li Int J Mol Sci. 2022 Jan 9;23(2):702. doi: 10.3390/ijms23020702.
Priming is an adaptive strategy that improves plant defenses against biotic and abiotic stresses. Stimuli from chemicals, abiotic cues, and pathogens can trigger the establishment of priming state. Priming with 5-aminolevulinic acid (ALA), a potential plant growth regulator, can enhance plant tolerance to the subsequent abiotic stresses, including salinity, drought, heat, cold, and UV-B. However, the molecular mechanisms underlying the remarkable effects of ALA priming on plant physiology remain to be elucidated. Here, we summarize recent progress made in the stress tolerance conferred by ALA priming in plants and provide the underlying molecular and physiology mechanisms of this phenomenon. Priming with ALA results in changes at the physiological, transcriptional, metabolic, and epigenetic levels, and enhances photosynthesis and antioxidant capacity, as well as nitrogen assimilation, which in turn increases the resistance of abiotic stresses. However, the signaling pathway of ALA, including receptors as well as key components, is currently unknown, which hinders the deeper understanding of the defense priming caused by ALA. In the future, there is an urgent need to reveal the molecular mechanisms by which ALA regulates plant development and enhances plant defense with the help of forward genetics, multi-omics technologies, as well as genome editing technology.