Uzoigwe Chika Edward
Department of Science, Medicine and Surgery, NHS England, London, United Kingdom.
Front Cell Dev Biol. 2025 Sep 11;13:1586481. doi: 10.3389/fcell.2025.1586481. eCollection 2025.
The advent of genetic technologies requires consideration of neo-microbes. Attention must first be given to mirror life-forms that exhibit chirality discordant to that prevalent in nature. It is important to understand the merits and challenges faced by "contra-lateralized" organisms. The hypothesis here is that such organisms would suffer almost insuperable disadvantages. Their energy transduction mechanisms would result in ATP hydrolysis. They would be vulnerable to both innate achiral and acquired bi-chiral host immunity, but their defense and virulence mechanisms would exhibit heterodox chirality and thus be ineffectual. They would be savagely out-competed by commensals. It is hypothesized that the greatest utility and threat is from "ambidextrous" species that exhibit chiral chimerism/chiral duality. Different functions would be executed by effectors of varying chirality which may be inducible or facultative. Such microbiota would show predominantly conventional biochemical "lateralization". However, few strategic functions would exhibit non-conformative chirality. One of the most significant dangers and potential benefits is the sheer unpredictability of the host response to counter-chiral antigens/molecules. Some synthetic enantiomers are an order of magnitude more active than their stereoisomer. Exceptional hazards thus lie in chiral chimeras that may elicit a hyper-exuberant immune reaction and shield themselves from that immune response by deploying a "cloaking" device in the form of a contra-chiral cell wall. As proof of this principle, cancer, which frequently overwhelms hosts, shows biochemical ambidexterity with bio-affinity for both L-glucose and D-glucose uptake and potentially also exploits D-amino acids for protein synthesis. Intriguingly, organisms of varying sophistication exhibit varying degrees of chiral duality. Hetero-chiral D-alanine and L-galactose derivates (fucose) and conjugate enzymes, for example, are bio-molecular protagonists. Extreme caution is required with such stereo-diverse agents, especially given that their chiral plasticity would be transmissible via plasmids or recombination, unlike obligate "mirror" species. However, effective regulation is fraught with obstacles as non-canonical chiral and bi-chiral enzymes and molecules already exist in nature, serving roles germane to species' survival. The fundamental question is whether there is a need for a critical threshold for the heterochiral metabolic enrichment of organisms beyond which a tangible hazard subsists.
基因技术的出现需要考虑新微生物。首先必须关注那些表现出与自然界普遍存在的手性不一致的镜像生命形式。了解“对侧化”生物体面临的优点和挑战很重要。这里的假设是,这类生物体将面临几乎无法克服的劣势。它们的能量转导机制将导致ATP水解。它们将易受先天非手性和后天双手机性宿主免疫的影响,但其防御和毒力机制将表现出非正统的手性,因此将无效。它们将被共生体残酷地淘汰。据推测,最大的效用和威胁来自表现出手性嵌合/手性二元性的“双手性”物种。不同的功能将由不同手性的效应器执行,这些效应器可能是可诱导的或兼性的。这类微生物群将主要表现出传统的生化“侧化”。然而,很少有战略功能会表现出不符合常规的手性。最重大的危险和潜在益处之一是宿主对反相手性抗原/分子反应的完全不可预测性。一些合成对映体比其立体异构体的活性高一个数量级。因此,特殊的危险在于手性嵌合体,它们可能引发过度旺盛的免疫反应,并通过部署反相手性细胞壁形式的“隐形”装置来保护自己免受免疫反应。作为这一原理的证明,经常使宿主不堪重负的癌症表现出生化上的双手性,对L-葡萄糖和D-葡萄糖的摄取具有生物亲和力,并且可能还利用D-氨基酸进行蛋白质合成。有趣的是,不同复杂程度的生物体表现出不同程度的手性二元性。例如,异手性D-丙氨酸和L-半乳糖衍生物(岩藻糖)以及共轭酶是生物分子的主角。对于这类立体多样的物质需要极其谨慎,特别是考虑到它们的手性可塑性可通过质粒或重组传递,这与专性“镜像”物种不同。然而,有效的监管充满障碍,因为自然界中已经存在非规范的手性和双手机性酶及分子,它们起着与物种生存相关的作用。根本问题是,生物体的异手性代谢富集是否需要一个临界阈值,超过这个阈值就会存在切实的危害。