Reflecting on Chiral Chimeric Cancer & Microbes: Ambidextrous Metabolism -the Real

Chika Edward Uzoigwe^*

• NHS England, London, United Kingdom

The advent of genetic technologies mandates 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-lateralised” organisms. The hypothesis here is that such organisms would suffer nigh-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 defence and virulence mechanisms would exhibit heterodox chirality and thus be ineffectual. They would be savagely out-competed by commensals. It is hypothesised 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. This may be inducible or facultative. Such microbiota would show predominantly conventional biochemical “lateralisation”. However, few strategic functions would exhibit non-conformative chirality. One of the most significant dangers and potential benefits is the sheer unpredictability regarding the host response to counter-chiral antigens/molecules. Some synthetic enantiomers are an order of magnitude more active than their stereoisomer. Exceptional thus hazards lie in chiral chimeras that may elicit a hyper-exuberant immune reaction and shield itself from that immune response by deploying a “cloaking” device in the form of 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 proteins synthesis. Intriguingly in nature organisms across the breadth of sophistication exhibit varying degrees of chiral duality. Hetero-chiral D-alanine and L-galactose derivates (fucose) and conjugate enzyme, for example, are bio-molecular protagonists.Extreme caution is required with such stereo-diverse agents, especially given that their subterfuge chiral plasticity would be transmissible via plasmids or recombination; unlike with 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 it is deemed a tangible hazard subsists.