The emergence of a new kind of biology.

'It is happily no longer axiomatic that a biophysicist is a physiologist who can fix his own amplifier. Fortunately, physicists are still drifting into biology and bringing new ideas. Please dear colleagues, do take the time to learn biochemistry.

What is an autotroph?

The concept of autotrophy depends on the growth media for pure cultures supplying a single one carbon source for anabolism. Secondary carbon compounds added to the medium as chelators and/or vitamins confuse the meaning. This note suggests a clarification of definition suitable for contemporary biochemical studies of true autotrophs.

Ligand field theory and the origin of life as an emergent feature of the periodic table of elements.

The assumption that all biological catalysts are either proteins or ribozymes leads to an outstanding enigma of biogenesis-how to determine the synthetic pathways to the monomers for the efficient formation of catalytic macromolecules in the absence of any such macromolecules. The last 60 years have witnessed chemists developing an understanding of organocatalysis and ligand field theory, both of which give demonstrable low-molecular-weight catalysts. We assume that transition-metal-ligand complexes are likely to have occurred in the deep ocean trenches by the combination of naturally occurring oceanic metals and ligands synthesized from the emergent CO(2), H(2), NH(3), H(2)S, and H(3)PO(4).

Analysis of the intermediary metabolism of a reductive chemoautotroph.

All extant life forms depend, directly or indirectly, on the autotrophic fixation of the dominant elements of the biosphere: carbon, hydrogen, nitrogen, oxygen, phosphorus, and sulfur. We have earlier presented the canonical network of reactions that constitute the anabolism of a reductive chemoautotroph. Separating this network into subgraphs reveals several empirical generalizations: (1) acetate (acetyl-CoA), pyruvate, phosphoenol pyruvate, oxaloacetate, and 2-oxoglutarate serve as universal starting points for all pathways leading to the universal building blocks-20 amino acids and 4 ribonucleotide triphosphates; (2) all pathways are anabolic; (3) all reactions operate by complete utilization of outputs with no molecules left behind as waste, ensuring conservation of information; (4) the core metabolome of 120 compounds is acidic, consisting of compounds containing phosphoric or carboxylic acid or both; and (5) the core network is both brittle-vulnerable to a single break-and robust-having persisted for 4 billion years.

The canonical network of autotrophic intermediary metabolism: minimal metabolome of a reductive chemoautotroph.

Chemoautorophs that fix carbon by the reductive tricarboxylic acid cycle represent one of the dominant bacterial life forms that make a major contribution to biomass production. From the viewpoint of biogenesis, construction of a canonical chart of intermediary metabolism for this class of organisms may help us to understand early cellular evolution and point us to the last universal common ancestor. Data-mining the KEGG Pathways database enabled us to integrate required biosynthetic pathways and derive a chart that represents the complete anabolic network of a reductive chemoautotroph.

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.

Ancient genes in contemporary persistent microbial pathogens.

Autotrophs, the earliest prokaryotes, use CO(2) as the sole or the key source in the reductive citric acid cycle for carbon fixation. This pathway, also known as the reductive tricarboxylic acid (rTCA) cycle, has as its center the Krebs cycle running in the reductive direction, using reduced cofactors for energy. During the infection process, persistent pathogenic bacteria like Mycobacterium tuberculosis, Helicobacter pylori, and Salmonella typhi experience diverse and hostile environments both intracellularly (in macrophages) and extracellularly.

A mechanism for the association of amino acids with their codons and the origin of the genetic code.

The genetic code has certain regularities that have resisted mechanistic interpretation. These include strong correlations between the first base of codons and the precursor from which the encoded amino acid is synthesized and between the second base of codons and the hydrophobicity of the encoded amino acid. These regularities are even more striking in a projection of the modern code onto a simpler code consisting of doublet codons encoding a set of simple amino acids.

Universality in intermediary metabolism.

We analyze the stoichiometry, energetics, and reaction concentration dependence of the reductive tricarboxylic acid (rTCA) cycle as a universal and possibly primordial metabolic core. The rTCA reaction sequence is a network-autocatalytic cycle along the relaxation pathway for redox couples in nonequilibrium reducing environments, which provides starting organic compounds for the synthesis of all major classes of biomolecules. The concentration dependence of its reactions suggests it as a precellular bulk process.

Spontaneous use of magnitude discrimination and ordination by the orangutan (Pongo pygmaeus).

The ability to discriminate quantity is descriptive of general cognitive ability. In this study, the authors presented 2 orangutans (Pongo pygmaeus) with a quantity judgment task. Each trial consisted of 2 choices, ranging from 1 to 6 food items in each.

The epistemic paradox of mind and matter.

The attempt to posit independent mind and matter results in an unavoidable circularity. We propose to accept this circularity and then explore the steps from the various "constructs" of matter to those biological structures associated with mind. This enables us to explore the hierarchical levels of emergence that take us from the periodic table of the elements to consciousness as it develops in the evolutionary radiation.

The origin of intermediary metabolism.

The core of intermediary metabolism in autotrophs is the citric acid cycle. In a certain group of chemoautotrophs, the reductive citric acid cycle is an engine of synthesis, taking in CO(2) and synthesizing the molecules of the cycle. We have examined the chemistry of a model system of C, H, and O that starts with carbon dioxide and reductants and uses redox couples as the energy source.

The synthesis of glutamic acid in the absence of enzymes: implications for biogenesis.

This paper reports on the non-enzymatic aqueous phase synthesis of amino acids from keto acids, ammonia and reducing agents. The facile synthesis of key metabolic intermediates, particularly in the glycolytic pathway, the citric acid cycle, and the first step of amino acid synthesis, lead to new ways of looking at the problem of biogenesis.