OF ALL THE PLAUSIBLE PREBIOTIC SOURCE MOLECULES CYANIDE AND ALDEHYDES ARE CONSIDERED THE SIMPLEST AND WIDELY PREVALENT. THE REACTIONS OF CYANIDE AND SIMPLE ALDEHYDES IN THE CONTEXT OF PREBIOTIC CHEMISTRY ARE PROPOSED TO HAVE PLAYED A MAJOR ROLE IN ACCUMULATING IMPORTANT PREBIOLOGICALLY RELEVANT BUILDING BLOCKS (NUCLEOBASES SUGARS HYDROXY ACIDS FATTY ACIDS AND AMINO ACIDS). HOWEVER FURTHER CHEMISTRIES OF THE THUS PRODUCED PRIMORDIAL BUILDING BLOCKS ARE USUALLY DEALT SEPARATELY IN ISOLATION FROM THE VERY PREBIOTIC MOLECULAR SOURCE MOLECULES THEY WERE PRODUCED FROM WHICH IS HIGHLY UNREALISTIC. SYSTEMS CHEMISTRY IS AN IMPORTANT CONCEPT THAT HAS TO BE RECKONED WITH IN PREBIOTIC CHEMISTRY ESPECIALLY GIVEN THE HETEROGENEOUS PRODUCT DISTRIBUTION THAT RESULTS IN ALMOST ALL OF THE PREBIOTIC REACTIONS (FOR EXAMPLE THE FORMOSE REACTION AND HCN POLYMERIZATION TO NAME A FEW). WE HYPOTHESIZE THAT UNDER SYSTEMS CHEMISTRY SCENARIOS THE SOURCE PREBIOTIC MOLECULES (SUCH AS CYANIDE AND FORMALDEHYDE) WOULD ALSO INTERACT WITH THEIR RESPECTIVE REACTION PRODUCTS AND LEAD TO PRODUCTIVE PRIMORDIAL REACTION PATHWAYS. SPECIFICALLY WE HYPOTHESIZE THAT THE TRANSFORMATIONS OF SIMPLE ALDEHYDES AND ALPHA-HYDROXY KETO ACIDS BY THEIR INTERACTION WITH CYANIDE (IN THE PRESENCE AND ABSENCE OF AMINO COMPOUNDS) WOULD LEAD TO ALTERNATIVE AND EXTANT BIOGENIC MOLECULES. WE PROPOSE TO SYSTEMATICALLY INVESTIGATE THE SCOPE OF THIS CYANIDE MEDIATED SYSTEMS CHEMISTRY WITH A VIEW TO DEVELOPING AN INVENTORY OF SYSTEMS CHEMISTRY REACTIONS (SUCH AS THE REACTIONS IN A REDUCTIVE CITRIC ACID CYCLE) THAT CAN BECOME SELF-SUSTAINING GIVEN A CONTINUOUS SUPPLY OF PREBIOTIC SOURCE MOLECULES. THIS WOULD SET THE STAGE FOR SYSTEMS CHEMISTRY TO TRANSFORM INTO PROTO-METABOLIC PATHWAYS. WE HAVE PROMISING PRELIMINARY RESULTS THAT LEND CREDENCE TO THE CYANIDE MEDIATED SYSTEMS CHEMISTRY HYPOTHESIS AND APPROACH. WE HAVE DISCOVERED THAT CYANIDE INTERACTS WITH MANY SMALL MOLECULES (SUCH AS FORMALDEHYDE AND GLYOXYLATE) GETS INCORPORATED AND HYDROLYZED TO YIELD A SUITE OF HYDROXY ACIDS THAT ARE CONSTITUENTS OF SOME OF THE METABOLIC CYCLES OF EXTANT BIOLOGY. MOREOVER BASED ON THE POTENTIAL TO TRANSFORM SUCH HYDROXY ACIDS TO KETO ACIDS WE PROPOSE THAT INTERACTION OF THESE KETO ACIDS WITH CYANIDE WOULD OPEN UP OPPORTUNITIES (SUCH AS REDUCTIVE CHEMISTRIES) THAT WERE NOT POSSIBLE PREVIOUSLY IN A PREBIOTIC CONTEXT. BASED ON THIS HYPOTHESIS WE HAVE DEVELOPED AN EFFICIENT CONVERSION OF AN ALPHA-KETO ACID (OXALA ACETATE) TO ITS CORRESPONDING ALPHA HYDROXY ACID (MALATE) UNDER POTENTIALLY PREBIOTIC CONDITIONS. THIS OBSERVATION ALSO OPENS UP A NOVEL REDUCTIVE AMINATION PROCESS THAT COULD CONVERT SELECTED ALPHA-KETO ACIDS TO THE CORRESPONDING ALPHA-AMINO ACIDS. THE DEMONSTRATION OF MANY OF THE KEY STEPS OF THE REDUCTIVE CITRIC ACID CYCLE THAT SO FAR HAS ELUDED EXPERIMENTAL DEMONSTRATION WOULD BECOME POSSIBLE BY EMPLOYING THIS CYANIDE MEDIATED CHEMICAL TRANSFORMATION REPETITIVELY. THIS PROPOSAL ADDRESSES THE PREBIOTIC EVOLUTION RESEARCH EMPHASIS OF EXOBIOLGY SPECIFICALLY RELATING TO THE MAJOR OBJECTIVE IN DETERMINING WHAT CHEMICAL SYSTEMS COULD HAVE SERVED AS PRECURSORS OF METABOLIC SYSTEMS ON EARTH AND/OR ELSEWHERE. THIS PROPOSAL ALSO EXPERIMENTALLY MODELS A TYPE OF EARLY ENVIRONMENT ON THE EARTH IN WHICH ORGANIC CHEMICAL SYNTHESIS COULD OCCUR IN THE CONTEXT OF PROTOMETABOLIC PATHWAYS.
$911,716FY2020National Aeronautics and Space AdministrationNASA
Scripps Research Institute, La Jolla CA