氨基酸的手性与蛋白质生物合成

生命体中行使生物学功能的重要大分子蛋白质,由其基本单位氨基酸组成. 除甘氨酸外,其余19种常见氨基酸均具有手性,且均为L-构型,称为氨基酸的纯手性（homochirality,或称同手性）.这个现象长久以来困扰着科学家们. 本文简要综述了目前对纯手性起源的一些假说,D-氨基酸在生命体中的存在和可能的作用,以及D-氨基酸在蛋白质合成这个重要过程中的特性,包括D-氨基酸的氨酰化和在新生肽链的掺入. D-氨基酸的研究,让人们对生命有了更深入的认识,为疾病、制药等领域提供了新的思路,也为生命科学的基础研究提供了新的理论支撑和研究方向.     

d-Amino acids in molecular evolution in space – Absolute asymmetric photolysis and synthesis of amino acids by circularly polarized light

Living organisms on the Earth almost exclusively use l-amino acids for the molecular architecture of proteins. The biological occurrence of d-amino acids is rare, although their functions in various organisms are being gradually understood. A possible explanation for the origin of biomolecular homochirality is the delivery of enantioenriched molecules via extraterrestrial bodies, such as asteroids and comets on early Earth. For the asymmetric formation of amino acids and their precursor molecules in interstellar environments, the interaction with circularly polarized photons is considered to have played a potential role in causing chiral asymmetry. In this review, we summarize recent progress in the investigation of chirality transfer from chiral photons to amino acids involving the two major processes of asymmetric photolysis and asymmetric synthesis. We will discuss analytical data on cometary and meteoritic amino acids and their potential impact delivery to the early Earth. The ongoing and future ambitious space missions, Hayabusa2, OSIRIS-REx, ExoMars 2020, and MMX, are scheduled to provide new insights into the chirality of extraterrestrial organic molecules and their potential relation to the terrestrial homochirality. This article is part of a Special Issue entitled: d-Amino acids: biology in the mirror, edited by Dr. Loredano Pollegioni, Dr. Jean-Pierre Mothet and Dr. Molla Gianluca.     

Origin of amino acid homochirality: relationship with the RNA world and origin of tRNA aminoacylation

The origin of homochirality of l-amino acids has long been a mystery. Aminoacylation of tRNA might have provided chiral selectivity, since it is the first process encountered by amino acids and RNA. An RNA minihelix (progenitor of the modern tRNA) was aminoacylated by an aminoacyl phosphate oligonucleotide that exhibited a clear preference for l- as opposed to d-amino acids. A mirror-image RNA system with l-ribose exhibited the opposite selectivity, i.e., it exhibited an apparent preference for the d-amino acid. The selectivity for l-amino acids is based on the stereochemistry of RNA. The side chain of d-amino acids is located much closer to the terminal adenosine of the minihelix, causing them collide and interfere during the amino acid-transfer step. These results suggest that the putative RNA world that preceded the protein theatre determined the homochirality of l-amino acids through tRNA aminoacylation.     

Deracemization of Amino Acids by Partial Sublimation and via Homochiral Self-Organization

Deracemization of a 50/50 mixture of enantiomers of aliphatic amino acids (Ala, Leu, Pro, Val) can be achieved by a simple sublimation of a pre-solubilized solid mixture of the racemates with a huge amount of a less-volatile optically active amino acid (Asn, Asp, Glu, Ser, Thr). The choice of chirality correlates with the handedness of the enantiopure amino acids—Asn, Asp, Glu, Ser, and Thr. The deracemization, enantioenrichment and enantiodepletion observed in these experiments clearly demonstrate the preferential homochiral interactions and a tendency of natural amino acids to homochiral self-organization. These data may contribute toward an ultimate understanding of the pathways by which prebiological homochirality might have emerged.     

Amino Acid Homochirality may be Linked to the Origin of Phosphate-Based Life

Phosphorylation has to have been one of the key events in prebiotic evolution on earth. In this article, the emergence of phosphoryl amino acid 5′-nucleosides having a P–N bond is described as a model of the origin of amino acid homochirality and Genetic Code. It is proposed that the intramolecular interaction between the nucleotide base and the amino acid side-chain influences the stability of particular amino acid 5′-nucleotides, and the interaction also selects for the chirality of amino acids. The differences between l- and d-conformation energies (ΔE _conf) are evaluated by DFT methods at the B3LYP/6-31G(d) level. Although, as expected, these ΔE _conf values are not large, they do give differences in energy that can distinguish the chirality of amino acids. Based on our calculations, the chiral selection of the earliest amino acids for l-enantiomers seems to be determined by a clear stereochemical/physicochemical relationship. As later amino acids developed from the earliest amino acids, we deduce that the chirality of these late amino acids was inherited from that of the early amino acids. This idea reaches far back into evolution, and we hope that it will guide further experiments in this area.     

The origin of life and the left-handed amino-acid excess: the furthest heavens and the deepest seas?

The origin of life is an extraordinary problem that leads back to the structure and dynamics of the cosmos and early development of organic molecules. Within that wider question lies an unsolved problem that has troubled biologists for 150 years. What is the origin of the dominant presence of left-handed stereoisomers of amino acids in nature even though their synthesis normally results in an equal mixture of the right- and left-handed molecular forms? We propose that asymmetric Earth rotation caused at dawn and dusk circularly polarized UV light (CPUVL) of opposite polarity and reversed temperature profiles in the oceans. Destruction of the d-isomer by CPUVL at dusk in a sea surface hotter than at dawn created a daily l-isomer excess protected from radiation by nightfall, preserved by down-flow (diffusive, mechanical) into cold, darker regions, eventually initiating an l-amino-acid excess embodied in early marine forms. Innumerable mechanisms have been proposed for the origin of l-chiral dominance in amino acids and none proven. Since the thalidomide tragedy, homochirality of amino acids has been a growing practical issue for medicine. Understanding its origin may bring further and unexpected benefits. It may also be a modest pointer to the possibility of positive answers to whether intelligent life will have the capacity to continue to protect itself from conditions inimical to survival.     

A new theoretical model for the origin of amino acid homochirality

Amino acid homochirality, as a unique behavior of life, could have originated synchronously with the genetic code. In this paper, phosphoryl amino-acid -5′-nucleosides with P－N bond are postulated to be a chiral origin model in prebiotic molecular evolution. The enthalpy change in the intramolecular interaction between the nucleotide base and the amino-acid side-chain determines the sta-bility of the particular complex, resulting in a preferred conformation associated with the chirality of amino acids. Based on the theoretical model, our experiments and calculations show that the chiral selection of the earliest amino acids for L-enantiomers seems to be a strict stereochemi-cal/physicochemical determinism. As other amino acids developed biosynthetically from the earliest amino acids, we infer that the chirality of the later amino acids was inherited from the precursor amino acids. This idea probably goes far back in history, but it is hoped that it will be a guide for further ex-periments in this area.     

A new theoretical model for the origin of amino acid homochirality

Amino acid homochirality, as a unique behavior of life, could have originated synchronously with the genetic code. In this paper, phosphoryl amino-acid-5′-nucleosides with P-N bond are postulated to be a chiral origin model in prebiotic molecular evolution. The enthalpy change in the intramolecular interaction between the nucleotide base and the amino-acid side-chain determines the stability of the particular complex, resulting in a preferred conformation associated with the chirality of amino acids. Based on the theoretical model, our experiments and calculations show that the chiral selection of the earliest amino acids for L-enantiomers seems to be a strict stereochemical/physicochemical determinism. As other amino acids developed biosynthetically from the earliest amino acids, we infer that the chirality of the later amino acids was inherited from the precursor amino acids. This idea probably goes far back in history, but it is hoped that it will be a guide for further experiments in this area.     

First Results of the RAMBAS Experiment on Investigation of the Radiation Mechanism of Chiral Influence

The first results of the RAdiation Mechanism of Biomolecular ASymmetry (RAMBAS) experiment on investigation of the radiation mechanism of the influence on chiral molecules, as a factor leading to origination of chiral asymmetry are presented. It was found that irradiation of simple achiral materials by a flux of electrons from radioactive source initiated the synthesis of amino acids, and it resulted in asymmetric degradation and chiral asymmetry in a racemic mixture of amino acids. The results obtained can be important for the solution of the origin-of-life and biological homochirality problems.     

Chromatographic separation as selection process for prebiotic evolution and the origin of the genetic code

A model for the evolution of a translation apparatus has been suggested where oligonucleotides in a hairpin conformation act as primordial adapters. Specifically activated amino acids are assumed to be attached to these hairpin molecules. For the specific activation, a chromatographic separation of, e.g. ala and CMP from gly and GMP can be accomplished on silica (e.g. of volcanic origin) with aqueous salt solutions. Other adsorbents like clays (kaolin, bentonite, montmorillonite), different silicates (florisil, magnesium trisilicate, calcium silicate, talc), hydroxyapatite, barium sulfate, calcium carbonate, calcium fluoride and titanoxide have been examined as model systems for the separation of nucleotides, nucleosides and amino acids on mineral surfaces. The possible role of chromatographic separation of amino acids for the formation of proteinoids, composed of selected amino acids, is also considered.     

D-Amino Acids in Living Higher Organisms

The homochirality of biological amino acids (L-amino acids) andof the RNA/DNA backbone (D-ribose) might have become establishedbefore the origin of life. It has been considered that D-aminoacids and L-sugars were eliminated on the primitive Earth.Therefore, the presence and function of D-amino acids in livingorganisms have not been studied except for D-amino acids in thecell walls of microorganisms. However, D-amino acids wererecently found in various living higher organisms in the form offree amino acids, peptides, and proteins. Free D-aspartate andD-serine are present and may have important physiologicalfunctions in mammals. D-amino acids in peptides are well knownas opioid peptides and neuropeptides. In protein, D-aspartateresidues increase during aging. This review deals with recentadvances in the study of D-amino acids in higher organisms.     

Epimerization of Alanyl-Alanine Induced by γ-Rays Irradiation in Aqueous Solutions

Living organisms have homochiral L-amino acids in proteins and homochiral D-mononucleotides in nucleic acids. The chemical evolutionary process to protein homochirality has been discussed for many years. Although many scenarios have been proposed for homochirality in the monomeric compounds, homochirality in amino acids and mononucleotides does not always guarantee homochirality in polypeptides and polynucleotides. Integrated scenarios containing the pathways from monomer to polymer should be proposed because in the pathways oligomers and polymers as well as monomers racemize (or epimerize), degrade, and condense. This research addresses epimerization and degradation of dipeptides under γ-rays irradiation by a cobalt-60 (⁶⁰Co) radiation source. The different rate constants of epimerization between diastereomeric dipeptides in the research suggest that the potential pathway toward homochirality could be much more complex.     

Results of the Second Stage of the Investigation of the Radiation Mechanism of Chiral Influence (RAMBAS-2 Experiment)

Results of the second stage of the RAMBAS (RAdiation Mechanism of Biomolecular ASymmetry) experiment on investigation of the radiation mechanism of the influence on chiral molecules are presented. Optical activity of samples of racemic mixtures of amino acids with heavy metals was compared prior to and after irradiation by electron flux from a radioactive source. It is found that the irradiation results in asymmetric degradation of both complexes and amino acids and in production of chiral asymmetry of the samples under study. These results confirm the conclusions inferred from the first stage of the RAMBAS experiment and could be important for the solution of the origin-of-life and biological homochirality problems.     

Amplification of Chirality at Solid Surfaces

Symmetry-breaking phenomena in two-dimensional crystallization at surfaces are reviewed and the potential impact to chiral amplification in three-dimensional systems in connection with the origin of homochirality in the biomolecular world is discussed. Adsorption of prochiral molecules leads to two-dimensional conglomerates, i.e., on a local scale spontaneously to homochiral crystal structures. Small enantiomeric excess or chiral impurities in this environment install homochirality on a global scale, that is, on the entire surface.     

On concerted origin of transfer RNAs with complementary anticodons

Pairs of antiparallelly oriented consensus tRNAs with complementary anticodons show surprisingly small numbers of mispairings within the 17-bp-long anticodon stem and loop region. Even smaller such complementary distances are shown by illegitimately complementary anticodons, i.e. those with allowed pairing between G and U bases. Accordingly, we suppose that transfer RNAs have emerged concertedly as complementary strands of primordial double helix-like RNA molecules. Replication of such molecules with illegitimately complementary anticodons might generate new synonymous codons for the same pair of amino acids. Logically, the idea of tRNA concerted origin dictates very ancient establishment of direct links between anticodons and the type of amino acids with which pre-tRNAs were to be charged. More specifically, anticodons (first of all, the 2nd base) could selectively target their amino acids, reaction of acylating itself being performed by another non-specific site of pre-tRNA or even by another ribozyme. In all, the above findings and speculations are consistent to the hypercyclic concept (Eigen and Schuster, 1979), and throw new light on the genetic code origin and associated problems. Also favoring this idea are data on complementary codon usage patterns in different genomes.     

The Role of Supernova Neutrinos on Molecular Homochirality

Electroweak parity violating interaction between supernova (SN) neutrinos and electrons of a simple chiral molecule is studied related to the origin of molecular homochirality. Appearance of supernova remnants inside molecular clouds favours the interaction of SN-neutrinos with interstellar molecules, leading to a energetic difference between the two enantiomers of the order of 10^–5 eV. This energetic difference is closer to the thermic energy of the interstellar medium, so molecular homochirality could be enhanced in molecular clouds containing supernova remnants inside it due to neutrino interaction.     

The origin of the RNA world: co-evolution of genes and metabolism

Discoveries demonstrating that RNA can serve genetic, catalytic, structural, and regulatory roles have provided strong support for the existence of an RNA World that preceded the origin of life as we know it. Despite the appeal of this idea, it has been difficult to explain how macromolecular RNAs emerged from small molecules available on the early Earth. We propose here a mechanism by which mutual catalysis in a pre-biotic network initiated a progression of stages characterized by ever larger and more effective catalysts supporting a proto-metabolic network, and the emergence of RNA as the dominant macromolecule due to its ability to both catalyze chemical reactions and to be copied in a template-directed manner. This model suggests that many features of modern life, including the biosynthetic pathways leading to simple metabolites, the structures of organic and metal ion cofactors, homochirality, and template-directed replication of nucleic acids, arose long before the RNA World and were retained as pre-biotic systems became more sophisticated.     

Racemization and the origin of optically active organic compounds in living organisms

The organic compounds synthesized in prebiotic experiments are racemic mixtures. A number of proposals have been offered to explain how asymmetric organic compounds formed on the Earth before life arose, with the influence of chiral weak nuclear interactions being the most frequent proposal. This and other proposed asymmetric syntheses give only slight enantiomeric excess and any slight excess will be degraded by racemization. This applies particularly to amino acids where half-lives of 10(5)-10(6) years are to be expected at temperatures characteristic of the Earth's surface. Since the generation of chiral molecules could not have been a significant process under geological conditions, the origins of this asymmetry must have occurred at the time of the origin of life or shortly thereafter. It is possible that the compounds in the first living organisms were prochiral rather than chiral; this is unlikely for amino acids, but it is possible for the monomers of RNA-like molecules.     

Selective chirality — A closer examination

The recent suggestion (Root-Bernstein, 1982) that the homochirality of amino acids and sugars in the current biosphere may have originated as a result of novel organic selector molecules is examined critically. It is concluded that such selector molecules are non-existent as described, and that their postulation is based on chemical and stereochemical misconceptions.