This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes. Review Cite This: Chem. Rev. 2020, 120, 4660−4689 pubs.acs.org/CR The Search for Chiral Asymmetry as a Potential Biosignature in our Solar System Daniel P. Glavin,*,† Aaron S. Burton,‡ Jamie E. Elsila,† José C. Aponte,†,§ and Jason P. Dworkin† †NASA Goddard Space Flight Center, Greenbelt, Maryland 20771, United States ‡NASA Johnson Space Center, Houston, Texas 77058, United States §Catholic University of America, Washington, D.C. 20064, United States ABSTRACT: The search for evidence of extraterrestrial life in our Solar System is currently guided by our understanding of terrestrial biology and its associated biosignatures. The observed homochirality in all life on Earth, that is, the predominance of “left-handed” or L-amino acids and “right-handed” or D-sugars, is a unique property of life that is crucial for molecular recognition, enzymatic function, information storage and structure and is thought to be a prerequisite for the origin or early evolution of life. Therefore, the detection of L- or D-enantiomeric excesses (ee) of chiral amino acids and sugars could be a powerful indicator for extant or extinct life on another world. However, studies of primitive meteorites have revealed they contain extraterrestrial amino acids and sugar acids (aldonic acids) with large enantiomeric excesses of the same chirality as terrestrial biology resulting from nonbiological processes, complicating the use of chiral asymmetry by itself as a definitive biosignature. Here we review our current knowledge of the distributions and enantiomeric and isotopic compositions of amino acids and polyols found in meteorites compared to terrestrial biology and propose a set of criteria for future life detection missions that can be used to help establish the origin of chiral asymmetry. CONTENTS Author Information 4680 Corresponding Author 4680 1. Introduction 4660 ORCID 4680 2. Amino Acids in Meteorites and Life 4664 Notes 4680 2.1. Abiotic Distributions and Formation Path- Biographies 4680 ways 4664 Acknowledgments 4681 2.2. Amino Acids in Terrestrial Biology 4667 References 4681 2.3. Amino Acid Racemization 4668 2.4. Amino Acid Asymmetry and Amplification Mechanisms 4668 3. Polyols in Meteorites and Life 4671 1. INTRODUCTION 3.1. Distributions and Formation Pathways 4671 The search for convincing evidence of extinct or extant signs of 3.2. Aldonic Acid Enantiomeric Excesses in life in our Solar System will require a suite of measurements Meteorites 4673 that focus on identifying characteristic features of life (i.e., 4. Isotopic Measurements of Amino Acids and potential biosignatures), establishing the environmental Polyols 4673 context for those measurements, a rigorous understanding of 4.1. Terrestrial vs Extraterrestrial Stable Isotopic potential terrestrial contamination, and knowledge of the Ratios 4673 processes that led to the origin of the biosignatures such that 4.2. Isotopes and Enantiomeric Excesses 4674 all plausible abiotic formation mechanisms can be ruled out. 5. Proposed Framework for Using Chirality as a Any life detection investigation should be focused on the key Biosignature 4674 molecular classes and properties at the core of terrestrial 5.1. Detection of Chiral Asymmetry 4674 biology, including a search for homochirality.1−3 Although its 5.2. Simple Distribution 4676 origin remains a mystery, biological homochirality (the 5.3. Isotopic Composition 4676 incorporation of L-amino acids in the production of genetically 6. Relevant Past, Current and Future Missions 4677 6.1. Comets 4677 6.2. Asteroid Sample Return and Ceres 4678 Special Issue: Chemical Evolution and the Origins of Life 6.3. Mars Exploration and Sample Return 4679 Received: July 26, 2019 7. Conclusions 4680 Published: November 19, 2019 © 2019 American Chemical Society 4660 DOI: 10.1021/acs.chemrev.9b00474 Chem. Rev. 2020, 120, 4660−4689 Chemical Reviews Review coded proteins and D-ribose and D-deoxyribose in nucleic and origins of life amino acid studies, here we also use D and acids, coenzymes, and metabolic feedstock) is thought to be a L.) Miller spark discharge experiments simulating primordial prerequisite for, or early product of, life. In terrestrial proteins, Earth conditions containing H2O, CH4, NH3, and H2S have enzymatic function is dependent on the folding of the amino produced 34 different two- to six-carbon protein and acid chain into a highly ordered structure, which is not possible nonprotein amino acids15−17 (Table 1)withrelative if the amino acids are racemic (equal amounts of both D- and L- abundances similar to those found in carbonaceous meteor- enantiomers). ites.17 Amino acid analyses of the Murchison CM2 type The majority of life on Earth uses L-amino acids and D- meteorite shortly after its fall and recovery in Southeastern sugars (Figure 1, Tables 1 and 2), although there are some rare Australia in 1969 also found that the chiral α-hydrogen protein amino acids were racemic, suggesting an extraterrestrial, abiotic origin.18,19 More recent amino acid analyses of Murchison and a variety of other carbonaceous meteorites have found L- enantiomeric excesses of several nonprotein α-dialkyl amino acids that are rare on Earth,20,21 including isovaline with 22−24 measured L-excesses as high as ∼20%. Based on these data, it has been proposed in NASA’s Ladder of Life Detection criteria that L- or D-enantiomeric excesses of >20% in multiple amino acids in an extraterrestrial sample would have a high likelihood of being a biosignature provided that systematic errors and other instrument measurement artifacts and terrestrial contamination could be ruled out.25 However, enantiomeric enrichments that exceed 20% have been reported Figure 1. Fischer projections denoting the chirality of a generic α- for some extraterrestrial chiral compounds; for example, amino acid and aldose (chiral carbons denoted with asterisks), where nonterrestrial L-aspartic acid and L-glutamic acid enantiomeric L-denotes left and D-denotes right. Based on naming convention for excesses of up to 60% in the ungrouped C2 Tagish Lake 26 amino acids, the assignment of D or L is based on the chirality of the meteorite, similarly large L-isoleucine and D-allo-isoleucine carbon closest to the carboxylic acid (by analogy to glyceraldehyde), excesses in two different CR2 carbonaceous chondrites,27 and whereas for sugars, D or L is assigned based on the chiral center farthest from the most oxidized carbon (in this figure, the aldehyde several nonterrestrial enantiopure (100% ee) D-sugar acids group). (hereafter, D-aldonic acids) were discovered in the Murchison meteorite,28 evidencing that abiotic mechanisms can also exceptions that add molecules of the opposite chirality for produce large enantiomeric enrichments for some chiral 4,5 specialized purposes. Since the individual L-andD- compounds. Therefore, the proposed ee criteria for using enantiomers of these chiral molecules have identical physical chirality as a chemical biosignature need to be revisited. and chemical properties, there appear to be no biochemical The growing body of evidence for large ee of amino acids 6 reasons why one enantiomer would be favored over the other. and aldonic acids in carbonaceous meteorites combined with Although most proteins based on L-amino acids that interact plausible prebiotic mechanisms for the production of chiral with sugar-containing substrates in biology evolved to asymmetry in interstellar environments29 and subsequent recognize D-sugars, experimental studies have shown that enantioenrichment of both amino acids and sugars under some naturally occurring proteins can also catabolize L- 22,30−33 7,8 aqueous conditions complicates the use of chiral sugars, so incorporation of amino acids and sugars of the opposite handedness in proteins and nucleic acids may not be asymmetry alone as a unique feature of life. This review does a strict requirement for life.9 Thus, it has been inferred that the not provide a detailed overview of the numerous characteristics selection of L-amino acids and D-sugars by life on Earth was a of “life as we know it” that have been described in detail as part 25 random process and that life elsewhere could be based on of the “Ladder of Life Detection” framework. The primary 10 either enantiomer. The detection of D-amino acid or L-sugar goal of this paper is to provide a new framework for enantiomeric excesses (ee) with the opposite handedness as life establishing the origin of enantiomeric excesses in amino on Earth would be a very strong indicator of extraterrestrial acids and sugars that includes several important caveats based biology that evolved from an independent origin, since a on our current understanding of prebiotic chemistry from both terrestrial origin could be ruled out and, as of yet, there are no meteorites and laboratory experiments. We begin by giving an known abiotic sources of D-amino acid (single asymmetric overview of extraterrestrial amino acids and polyols (aldoses, carbon) or L-sugar excesses within our Solar System (Section aldonic acids, alditols, etc.) that have been identified in 2.3). meteorites and compare their distributions, enantiomeric In stark contrast to terrestrial biology, laboratory chemistry ratios, and isotopic compositions to those found in terrestrial experiments conducted under a range of plausible prebiotic conditions11−15 have shown that chiral species formed