Biological molecules are the building blocks of the cell, and with the advent of modern technologies, various biological molecules have been discovered.
By Kashif Hussaina, Maria Kausara, Talha Khanb , Mahad Khanc, Aqdas-Ul-Hassand
A summary of discoveries
Recent research has identified two new amino acids: selenocysteine (Sec) and pyrrolysine (Pyl) amino acids. A PI (18:1/18:1), an SCD1-derived lipid, has been discovered that limits stress signalling. A new carbohydrate, Glucoxylan (methyl-phenyl-formamide), has been explored in glycosylation. Various enzymes, including PETase, MHETase, poly(ADP-ribose) polymerase 1, and ADP-ribosyl transferase enzyme, has been discovered along with their novel applications. TIGER domain, or fierce, a new cellular organelle, has been found in recent years. A small ribbon-like glycol RNA has been discovered with novel applications in the glycosylation process. Rivilla and coworkers discovered Huisgenase activity-based biomolecules. It can be concluded that many biological molecules, enzymes and organelles exist in nature and need to be explored with the help of modern omics and advanced microscopic and molecular tools.
Selenocysteine
Selenocysteine, structurally aligned with cysteine, was discovered in an E. coli model in the 1980s and had a UGA mRNA codon. The 21st proteinogenic amino acid is selenocysteine (symbol Sec or U, often written as Se-Cys in earlier publications). Selenocysteine residues can be found in selenoproteins. An analogue of the more popular cysteine, selenocysteine substitutes selenium for sulphur. Numerous enzymes, including glutathione peroxidases, thioredoxin reductases, formate dehydrogenases, glycine reductases, selenophosphate synthetase 2, methionine-R-sulfoxide reductase B1 (SEPX1), and certain hydrogenases, contain selenium. It takes place in all three spheres of existence.
Selenocysteine (Sec), a 21st amino acid, was discovered by Dr. Dieter Söll, at Yale University in New Haven, Conn. Another Biochemist Thressa Stadtman at the National Institutes of Health, discovered selenocysteine. Sec plays a fundamental role in the homeostasis of selenium and maintains the overall metabolic rate
Pyrrolysine
Pyrrolysine (Pyl), 22nd amino acid with a pyrroline ring at the end of the lysin chain, was discovered in archaea and bacteria and encoded by UAG mRNA codon. Dr. Joseph Krzycyki and Michael Chan discovered L-pyrrolysine at Ohio State University in 2002.
Pyrrolysine is a -amino acid employed in the production of proteins in some methanogenic archaea and bacteria; it is devoid in humans, represented by the ‘amber’ stop codon (UAG). It contains an amino group, which under biological conditions is protonated and takes the form -NH+ 3; it also includes a carboxylate group, which under natural circumstances is deprotonated and takes the form -COO. Its pyrroline side chain is basic and positively charged at neutral pH, like lysine.
Plastic Degrading Enzymes
Ideonella sakaiensis is a bacterium that can degrade and consume plastic polyethene terephthalate (PET) by utilizing it as a carbon and energy source. It belongs to the genus Ideonella and the family Comamonadaceae. The bacterium was first discovered in a soil sample collected in Sakai City near a plant for recycling plastic bottles.
The PET hydrolase, or PETase, which is secreted from the Ideonella sakaiensis PET surface, breaks down the PET into mono(2-hydroxyethyl)terephthalic acid (MHET), a heterodimer made of terephthalic acid (TPA) and ethylene glycol. The PETase also breaks down PET into another intermediate called Bis-(2-hydroxyethyl) terephthalate (BHET), which can be broken down further into MHET. The I. sakaiensis PETase hydrolyzes the high-specificity ester bonds in PET to carry out its function. A lipid-anchored MHET hydrolase enzyme, or MHETase, on the cell’s outer membrane then breaks down the resultant MHET into its two monomeric components. PETase and MHETase were discovered in the bacterium and, based on their activity, were called TPADO.
PETase and MHETase were discovered by Professor Jen DuBois, Montana State University and Professor John McGeehan from the University of Portsmouth in 2018. Such enzymes are useful for recycling plastic material and polythene bags. Specifically, these enzymes break the TPA and ethylene glycol, a building block of PET polymer.
Ideonella sakaiensis’s finding may be significant for the breakdown of PET polymers. Before its discovery, few bacteria and fungus, such as Fusarium solani, were the only known PET degraders. It was not known that any organisms could use PET as a primary carbon and energy source. The discovery of I. sakaiensis sparked discussions about PET biodegradation as a technique for recycling and bioremediation.
Other Enzymes
Cardamone and coworkers (BUSM researchers) discovered the ADP-ribosyl transferase enzyme that plays a pivotal role in other protein alterations, and its activity was named NEURL4. Poly(ADP-ribosyl)transferase, mutates a variety of nuclear proteins by poly(ADP-ribosyl)nations. The alteration depends on DNA and is implicated in regulating several cellular processes like proliferation, differentiation, and mutations. It also regulates molecular events involved in retrieving cells from DNA damage.
Lipid: A SCD1-derived adipokine PI (18:1/18:1)
Thurmer and coworkers discovered an SCD1-derived adipokine PI (18:1/18:1) in 2022 that limits stress signalling by unsaturation of fatty acids, cytotoxic stress prevention, initiation of adaptive mechanisms, and programmed cell death. The lipid minimizes tumorigenesis stress, infections, chemoresistance, immune ageing, and fat diet.
The unfolded protein response (UPR) and autophagy are two adaptive mechanisms that are started by cytotoxic stress. It also causes programmed cell death. Although the mechanisms are complex, stearoyl-CoA desaturase (SCD)1 regulates fatty acid unsaturation, which reduces cytotoxic stress. The 1,2-dioleoyl-sn-glycero-3-phospho-(1′-myo-inositol) [PI(18:1/18:1)] is a signalling lipid derived from SCD1 that inhibits p38 mitogen-activated protein kinase activation, inhibits UPR, counteracts endoplasmic reticulum-associated protein degradation and apoptosis, regulates during the early stages of cell death, SCD1 expression and the cellular PI(18:1/18:1) fraction decline, which inhibits protein phosphatase 2 A and boosts stress signalling. Multiple human and animal cell lines, as well as tissues from Scd1-deficient mice, include this counter-regulation, which applies to various mechanistically distinct situations that cause death. The ratios of relative stress tolerance in carcinogenesis, chemoresistance, infection, high-fat diet, and immunological ageing are reflected in PI(18:1/18:1). A lipokine called PI(18:1/18:1) connects fatty acid unsaturation with stress responses, and its depletion triggers stress signalling.
Glucoxylan: A new carbohydrate molecule
Glucoxylan, a new type of polysaccharide, is a combination of glucose and xylose—a rare combination though both are present separately in all cereals. The same carbohydrate has been found in marine algae. Codee and colleagues discovered methyl-phenyl-formamidine (a carbohydrate), which portrays a pivotal role in glycosylation following triggering in thiophilic and metal-assisted pathways. Allan and colleagues discovered a new carbohydrate in barley at the University of Adelaide 2022.
Glyco-RNA: A new RNA molecule
Glyco-RNA has been discovered by researchers at Stanford University and plays a pivotal role in living organisms. The molecules modify proteins and lipids during the glycosylation process.
Rivilla and coworkers discovered Huisgenase activity-based biomolecules. As they enabled the development of life as we know it, the emergence of nucleic acids and proteins has occasionally been referred to as the first and second evolution revolutions. According to some researchers, glycosylation, or the attachment of glycans to other biopolymers, ought to be ranked third because it enables cells to create a wide range of molecular shapes using the same DNA blueprints. Long thought to only be applied to proteins and lipids, an article published in Cell on May 17 expands on a preprint published in 2019 bioRxiv to argue that RNAs can also be glycosylated and that these sugar-coated nucleic acids seem to localize to cell membranes.
The recently discovered biological molecules are crucial components of various biological mechanisms and pathways. They open new ways or research opportunities in physiological mechanisms. Such discoveries disclose the different pathological mechanisms and are pivotal in controlling numerous deadly diseases like cancer. Detailed studies of these chemical molecules are lacking. There is a need to explore new biological molecules and applications of existing bio-molecules for the welfare of living organisms.
References (MLA-style)
Blackman, Stuart. “Discovering the 21st amino acid… again?.” The Scientist 18.19 (2004): 22-23.
Cardamone, Maria Dafne, et al. “Neuralized-like protein 4 (NEURL4) mediates ADP-ribosylation of mitochondrial proteins.” Journal of Cell Biology 221.3 (2022): e202101021.
Chen, Yingshan et al. “DNA Repair Factor Poly(ADP-Ribose) Polymerase 1 Is a Proviral Factor in Hepatitis B Virus Covalently Closed Circular DNA Formation.” Journal of virology vol. 96,13 (2022): e0058522.
Esposito, Mark, et al. “TGF-β-induced DACT1 biomolecular condensates repress Wnt signalling to promote bone metastasis.” Nature cell biology 23.3 (2021): 257-267.
Flynn, Ryan A., et al. “Small RNAs are modified with N-glycans and displayed on the surface of living cells.” Cell 184.12 (2021): 3109-3124.
Gallyas Jr, Ferenc, and Balazs Sumegi. “Mitochondrial protection by PARP inhibition.” International Journal of Molecular Sciences 21.8 (2020): 2767.
Kincannon, William M., et al. “Biochemical and structural characterization of an aromatic ring–hydroxylating dioxygenase for terephthalic acid catabolism.” Proceedings of the National Academy of Sciences 119.13 (2022): e2121426119.
Little, Alan, et al. “A novel (1, 4)-β-linked glucoxylan is synthesized by members of the cellulose synthase-like F gene family in land plants.” ACS central science 5.1 (2019): 73-84.
Ma, Weirui, and Christine Mayr. “A membraneless organelle associated with the endoplasmic reticulum enables 3′ UTR-mediated protein-protein interactions.” Cell 175.6 (2018): 1492-1506.
Rivilla, Iván, et al. “Discovering biomolecules with huisgenase activity: designed repeat proteins as biocatalysts for (3+ 2) cycloadditions.” Journal of the American Chemical Society 142.2 (2019): 762-776.
Thürmer, Maria, et al. “PI (18: 1/18: 1) is a SCD1-derived lipokine that limits stress signaling.” Nature Communications 13.1 (2022): 1-21.
Yarnell, Amanda. “22nd amino acid identified.” Chemical & Engineering News 80.21 (2002): 13-13.
Authors:
Kashif Hussaina, Maria Kausara, Talha Khanb , Mahad Khanc, Aqdas-Ul-Hassand
a: Department of Parasitology, University of Agriculture Faisalabad, Pakistan.
b: Department of Applied Chemistry, Government College University Faisalabad, Pakistan.
c: Department of food Sciences, Hungarian University of Agriculture and Life Sciences, Hungary
d: Independent Author