No Life on this Planet Without PHB

Abstract

The history of discovery by Rosetta Reusch of oligo-and poly-β-hydroxybutyrates (OHBs and PHBs) consisting of less than ca. 150 HB units is described. These 'short-chain' biopolymers can be detected in all living organisms and have numerous physiological activities of fundamental importance for the chemistry of life. The largest are components of ion channels such as Ca 2 + -polyphosphate-PHB (Ca-PPi-PHB) in genetically competent E. coli and in mammalian mitochondria. Sequences with chain lengths < ca. 30 occur covalently attached to proteins (posttranslational PHBylation), and methyl esters of the dimer and trimer are used by certain bacteria as highly efficient antioxidants. With synthetic monodisperse OHBs (up to 128mer) our group has contributed structural investigations, and we have shown that OHBs � 16 alone make phospholipid bilayer vesicles permeable to Ca ions. An extensive biochemical analysis of the TRPM8 protein channel, responsible for the sense of heat in our skin, proved to be fully active only when PHBylated. Reasons for the difficulty of detecting OHBs and PHBs are discussed: the polyester chain is highly flexible, and there is ester cleavage by base, acid, nucleophiles, Lewis acids, and heat -in stark contrast to peptides. PHBs may be called a ubiquitous but fleeting species in the chemistry of life -worth being appreciated and studied much more intensively in the future! A speculation about PHB's possible role in prebiotic compartmentalization is presented, and recent uses of compartmentalization in organic synthesis are briefly mentioned. Portions of the figures used herein were presented in a lecture at the International Symposium on Biopolymers on September 13, 2022, in Sion (Switzerland).

Recent Advancements in the Utilization of s-Block Organometallic Reagents in Organic Synthesis with Sustainable Solvents

“…For sure, the structure and dynamical properties of water and DESs are more complex than expected, and reactions of polar organometallic compounds of s-block elements across the "oil-water/DES" interface may represent another example of compartmentalization in organic synthesis [105]. Indeed, the use of Interphase-Rich Aqueous Systems (IRAS) are known to promote and guide organic reactions [106].…”

Open Questions about the Roles of DnaA, Related Proteins, and Hyperstructure Dynamics in the Cell Cycle

“…The many possible post-translational modifications to DnaA and to other proteins in the initiation and replication hyperstructures, therefore, include phosphorylation, and several other modifications, such as succinylation, methylation, proprionylation, malonylation, deamidation of asparagines, and glycosylation (for references see [ 69 ]). Another post-translational modification—and one that is largely ignored—is the covalent addition of poly-(R)-3-hydroxybutyrate (PHB) to proteins [ 74 ]; one proposed function of such addition to NAPs would be to regulate their interaction with nucleic acids [ 75 ]. An important question is, therefore, whether DnaA undergoes modifications like the addition of PHB and, if so, does such modification help the type of hyperstructure into which DnaA assembles?…”