- BS in Chemistry Education. Seoul National University, South Korea (1991)
- MS in Chemistry. Seoul National University, South Korea (1993)
- PhD in Chemistry. University of Alabama, Tuscaloosa, AL (2004)
- Postdoctoral Research Associate. University of Georgia, Athens, GA (2004-2006)
Darwinian Chemistry. RNA is thought to be the only genetic material on early Earth until DNA emerged. I am trying to get an RNA molecule that catalyzes the template-directed synthesis of RNA.
Dynamic Combinatorial Chemistry. Detection of specific nucleic acid sequence in complex genomic mixture is an important area. For this goal, I am using two oligonucleotide primers which can bind reversibly each other at the end of their sequence. These segmented primers are expected to prime in the presence of the target sequence without mismatch problem.
Catalytic Synthesis of Polyribonucleic Acid on Prebiotic Rock Glasses
Craig A. Jerome, Hyo-Joong Kim, Stephen J. Mojzsis, Steven A. Benner, and Elisa Biondi
Reported here are experiments that show that ribonucleoside triphosphates are converted to polyribonucleic acid when incubated with rock glasses similar to those likely present 4.3-4.4 billion years ago on the Hadean Earth surface, where they were formed by impacts and volcanism. This polyribonucleic acid averages 100-300 nucleotides in length, with a substantial fraction of 3',-5'-dinucleotide linkages. Chemical analyses, including classical methods that were used to prove the structure of natural RNA, establish a polyribonucleic acid structure for these products. The polyribonucleic acid accumulated and was stable for months, with a synthesis rate of 2 x 10-3 pmoles of triphosphate polymerized each hour per gram of glass (25°C, pH 7.5). These results suggest that polyribonucleotides were available to Hadean environments if triphosphates were. As many proposals are emerging describing how triphosphates might have been made on the Hadean Earth, the process observed here offers an important missing step in models for the prebiotic synthesis of RNA.
Abiotic Synthesis of Nucleoside 5'-Triphosphates with Nickel Borate and Cyclic Trimetaphosphate (CTMP)
Kim, H.J.., Benner, S.A.
(2021) 21(3), DOI:10.1089/ast.2020.2264
While nucleoside 5'-triphosphates are precursors for RNA in modern biology, the presumed difficulty of making these triphosphates on Hadean Earth has caused many prebiotic researchers to consider other activated species for the prebiotic synthesis of RNA. We report here that nickel(II), in the presence of borate, gives substantial amounts (2–3%) of nucleoside 5'-triphosphates upon evaporative heating in the presence of urea, salts, and cyclic trimetaphosphate (CTMP). Also recovered are nucleoside 5'-diphosphates and nucleoside 5'-monophosphates, both likely arising from 5'-triphosphate intermediates. The total level of 5'-phosphorylation is typically 30%. Borate enhances the regiospecificity of phosphorylation, with increased amounts of other phosphorylated species seen in its absence. Experimentally supported paths are already available to make nucleosides in environments likely to have been present on Hadean Earth soon after a midsized 1021 to 1023 kg impactor, which would also have delivered nickel to the Hadean surface. Further, sources of prebiotic CTMP continue to be proposed. Thus, these results fill in one of the few remaining steps needed to demystify the prebiotic synthesis of RNA and support a continuous model from atmospheric components to oligomeric RNA that is lacking only a mechanism to obtain homochirality in the product RNA.
When Did Life Likely Emerge on Earth in an RNA-First Process?
S. A. Benner, E. A. Bell, E. Biondi, R. Brasser, T. Carell, H.-J. Kim, S. J. Mojzsis, A. Omran, M. A. Pasek, D. Trail
2 , Chemistry Europe (2020) e1900035
The widespread presence of ribonucleic acid (RNA) catalysts and cofactors in the Earth's biosphere today suggests that RNA was the first biopolymer to support Darwinian evolution. However, most "path-hypotheses" to generate building blocks for RNA require reduced nitrogen-containing compounds not made in useful amounts in the CO2-N2-H2O atmospheres of the Hadean. We review models for Earth's impact history that invoke a single ~1023 kg impactor (Moneta) to account for measured amounts of platinum, gold, and other siderophilic ("iron-loving") elements on the Earth and Moon. If it were the last sterilizing impactor, by reducing the atmosphere but not the mantle Moneta, would have opened a "window of opportunity" for RNA synthesis, a period when RNA precursors rained from the atmosphere onto land holding oxidized minerals that stabilize advanced RNA precursors and RNA. Surprisingly, this combination of physics, geology, and chemistry suggests a time when RNA formation was most probable, ~120±100 million years after Moneta's impact, or ~4.36±0.1 billion years ago. Uncertainties in this time are driven by uncertainties in rates of productive atmosphere loss and amounts of sub-aerial land.
Chemical guidance in the search for past and extant life on Mars. Decadal Survey in Planetary Sciences and Astrobiology
Benner, S. A., Biondi, E., Kim, H.-J., Spacek, J.
Bulletin of the AAS
, AAS (2020) 53(4), DOI:10.3847/25c2cfeb.266df7e7
NASA should design missions to Mars to generate "Aha!" jolts for scientists researching the molecular origins of life. Recent advances allow these missions to be informed via privileged chemistry that likely generated RNA prebiotically on Earth, as well as general rules that constrain the structure of genetic molecules of extant life on Mars.
Hachimoji DNA and RNA: A genetic system with eight building blocks
Hoshika H, Leal N, Kim MJ, Kim MS, Karalkar NB, Kim HJ, Bates AM, Watkins Jr. NE, SantaLucia HA, Meyer AJ, DasGupta S, Piccirilli JA, Ellington AD, SantaLucia Jr. J, Georgiadis MM, Benner SA
(2019) 22 Feb 2019: Vol. 363, Issue 6429, pp. 884-887. DOI: 10.1126/science.aat0971
We report DNA- and RNA-like systems built from eight nucleotide "letters" (hence the name "hachimoji") that form four orthogonal pairs. These synthetic systems meet the structural requirements needed to support Darwinian evolution, including a polyelectrolyte backbone, predictable thermodynamic stability, and stereoregular building blocks that fit a Schrödinger aperiodic crystal. Measured thermodynamic parameters predict the stability of hachimoji duplexes, allowing hachimoji DNA to increase the information density of natural terran DNA. Three crystal structures show that the synthetic building blocks do not perturb the aperiodic crystal seen in the DNA double helix. Hachimoji DNA was then transcribed to give hachimoji RNA in the form of a functioning fluorescent hachimoji aptamer. These results expand the scope of molecular structures that might support life, including life throughout the cosmos.
Prebiotic Chemistry that Could Not Not Have Happened
Benner S.A., Kim H.-J., and Biondi E.
9 (4) , MDPI 84 (2019) https://doi.org/10.3390/life9040084
We present a direct route by which RNA might have emerged in the Hadean from a fayalite-magnetite mantle, volcanic SO2 gas, and well-accepted processes that must have created substantial amounts of HCHO and catalytic amounts of glycolaldehyde in the Hadean atmosphere. In chemistry that could not not have happened, these would have generated stable bisulfite addition products that must have rained to the surface, where they unavoidably would have slowly released reactive species that generated higher carbohydrates. The formation of higher carbohydrates is self-limited by bisulfite formation, while borate minerals may have controlled aldol reactions that occurred on any semi-arid surface to capture that precipitation. All of these processes have well-studied laboratory correlates. Further, any semi-arid land with phosphate should have had phosphate anhydrides that, with NH3, gave carbohydrate derivatives that directly react with nucleobases to form the canonical nucleosides. These are phosphorylated by magnesium borophosphate minerals (e.g., luneburgite) and/or trimetaphosphate-borate with Ni2+ catalysis to give nucleoside 5'-diphosphates, which oligomerize to RNA via a variety of mechanisms. The reduced precursors that are required to form the nucleobases came, in this path-hypothesis, from one or more mid-sized (1023-1020 kg) impactors that almost certainly arrived after the Moon-forming event. Their iron metal content almost certainly generated ammonia, nucleobase precursors, and other reduced species in the Hadean atmosphere after it transiently placed the atmosphere out of redox equilibrium with the mantle. In addition to the inevitability of steps in this path-hypothesis on a Hadean Earth if it had semi-arid land, these processes may also have occurred on Mars. Adapted from a lecture by the Corresponding Author at the All-Russia Science Festival at the Lomonosov Moscow State University on 12 October 2019, and is an outcome of a three year project supported by the John Templeton Foundation and the NASA Astrobiology program. Dedicated to David Deamer, on the occasion of his 80th Birthday.
Hydroxymethanesulfonate from volcanic sulfur dioxide. A mineral reservoir for formaldehyde in prebiotic chemistry.
Kawai, J., McLendon, D.C., Kim, H.-J., Benner, S.A.
(2019) 19(4):506-516, DOI:10.1089/ast.2017.1800
While formaldehyde (HCHO) was likely generated in Earth's prebiotic atmosphere by ultraviolet light, electrical discharge, and/or volcano-created lightning, HCHO could not have accumulated in substantial amounts in prebiotic environments, including those needed for prebiotic processes that generate nucleosidic carbohydrates. HCHO at high concentrations in alkaline solutions self-reacts in the Cannizzaro reaction to give methanol and formate, neither having prebiotic value. Here, we explore the possibility that volcanic sulfur dioxide (SO2) might have generated a reservoir for Hadean HCHO by a reversible reaction with HCHO to give hydroxymethanesulfonate (HMS). We show that salts of HMS are stable as solids at 90°C and do not react with themselves in solution, even at high (>8 M) concentrations. This makes them effective stores of HCHO, since the reverse reaction slowly delivers HCHO back into an environment where it can participate in prebiotically useful reactions. Specifically, we show that in alkaline borate solutions, HCHO derived from HMS allows formation of borate-stabilized carbohydrates as effectively as free HCHO, without losing material to Cannizzaro products. Further, we show that SO2 can perform similar roles for glycolaldehyde and glyceraldehyde, two intrinsically unstable carbohydrates that are needed by various models as precursors for RNA building blocks. Zircons from the Hadean show that the Hadean mantle likely provided volcanic SO2 at rates at least as great as the rates of atmospheric HCHO generation, making the formation of Hadean HMS essentially unavoidable. Thus, hydroxymethylsulfonate adducts of formaldehyde, glycolaldehyde, and glyceraldehyde, including the less soluble barium, strontium, and calcium salts, are likely candidates for prebiotically useful organic minerals on early Earth.
A Prebiotic Synthesis of Canonical Pyrimidine and Purine Ribonucleotides
Kim, H.-J., Kim, J.
(2019) 19(5):669-74, DOI:10.1089/ast.2018.1935
The "RNA first" model for the origin of life holds that RNA emerged spontaneously on early Earth and developed into life through its dual capabilities for genetics and catalysis. The model's central weakness is the difficulty of making its building blocks, in particular, the glycosidic bond joining nucleobases to ribose. Thus, the focus of much of the modern literature on the topic is directed toward solving this difficulty and includes elegant, though indirect, methods for making this bond. Here, we report that the glycosidic bond in canonical pyrimidine and purine ribonucleotides can be formed by direct coupling of cyclic carbohydrate phosphates with free nucleobases, all reported to be available by experimentally supported pathways that might have operated on early Earth.
A Direct Prebiotic Synthesis of Nicotinamide Nucleotide
Hyo-Joong Kim, Steven A. Benner
, Wiley-VCH (2018) Jan 12;24(3):581-584. doi: 10.1002/chem.201705394
Under the "RNA World" hypothesis, an early episode of
natural history on Earth used RNA as the only genetically encoded
molecule to catalyze steps in its metabolism catalysis. This, according
to the hypothesis, included RNA catalysts that used RNA cofactors.
However, the RNA World hypothesis places special demands on
prebiotic chemistry, which must now deliver not only four
ribonucleosides, but also must deliver the "functional" portion of these
RNA cofactors. While some (e.g. methionine) present no particular
challenges, nicotinamide ribose is special. Essential to its role in
biological oxidations and reductions, its glycosidic bond that holds a
positively charged heterocycle is especially unstable with respect to
cleavage. Nevertheless, we are able to report here a prebiotic
synthesis of phosphorylated nicotinamide ribose under conditions that
also conveniently lead to the adenosine phosphate components of
this and other RNA cofactors.
Mineral-Organic Interactions in Prebiotic
Synthesis. The Discontinuous Synthesis Model for the Formation of RNA in Naturally Complex Geological Environments.
Steven A. Benner, Hyo-Joong Kim, and Elisa Biondi
Nucl. Acids & Mol. Bio.
35 , Springer 31-83 (2018) https://doi.org/10.1007/978-3-319-93584-3_3
A common criticism of "prebiotic chemistry research" is that it is done
with starting materials that are too pure, in experiments that are too directed, to get
results that are too scripted, under conditions that could never have existed on Earth.
Planetary scientists in particular remark that these experiments often arise simply
because a chemist has a "cool idea" and then pursues it without considering external
factors, especially geological and planetary context. A growing literature addresses
this criticism and is reviewed here. We assume a model where RNA emerged
spontaneously from a prebiotic environment on early Earth, giving the planet its
first access to Darwinism. This "RNA First Hypothesis" is not driven by the intrinsic
prebiotic accessibility; quite the contrary, RNA is a "prebiotic chemist's nightmare."
However, by assuming models for the accretion of the Earth, the formation of the
Moon, and the acquisition of Earth's "late veneer," a reasonable geological model
can be envisioned to deliver the organic precursors needed to form the nucleobases
and ribose of RNA. A geological model having an environment with dry arid land
under a carbon dioxide atmosphere receiving effluent from serpentinizing igneous
rocks allows their conversion to nucleosides and nucleoside phosphates. Mineral
elements including boron and molybdenum prevent organic material from devolving
to form "tars" along the way. And dehydration and activation allows the formation of
oligomeric RNA that can be stabilized by adsorption on available minerals.
(View publication page for Hyo-Joong Kim)
- Synthetic biology
- Synthetic organic chemistry
- Organometallic catalysis
- Medicinal chemistry