Calcium in biological systems

A model is proposed for the mechanism of flocculation interactions in yeasts in which flocculent cells have a recognition factor which attaches to alpha-mannan sites on other cells. This factor may be governed by the expression of the single, dominant gene FLO1. Isogenic strains of Saccharomyces cerevisiae, differing only at FLO1 and the marker genes ade1 and trp1, were developed to examine the components involved in flocculene. Electron microscopy and concanavalin Aferritin labeling of aggregated cells showed that extensive and intense interactions between cell wall mannan layers mediated cell aggregation. The components of the mannan layer essential for flocculence were Ca2+ ions, alpha-mannan carbohydrates, and proteins. By studying the divalent cation dependence at various pH values and in the presence of competing monovalent cations, flocculation was found to be Ca2+ dependent; however, Mg2+ and Mn2+ ions substituted for Ca2+ under certain conditions. Reversible inhibition of flocculation by concanavalin A and succinylated concanavalin A implicated alpha-branched mannan carbohydrates as one essential component which alone did not determine the strain specificity of flocculence, since nonflocculent strains interacted with and competed for binding sites on flocculent cells. FLO1 may govern the expression of a proteinaceous, lectin-like activity, firmly associated with the cell walls of flocculent cells, which bind to the alpha-mannan carbohydrates of adjoining cells. It was selectively and irreversibly inhibited by proteolysis and reduction of disulfide bonds. The potential of this system as a model for the genetic and biochemical control of cell-cell interactions is discussed.

Possible mechanism for flocculation interactions governed by gene FLO1 in Saccharomyces cerevisiae.

While natural and synthetic N-nucleosides are vulnerable to enzymatic and acid-catalyzed hydrolysis of the nucleosidic bond, their C-analogues are much more stable. Several C-nucleosides are naturally occurring compounds, e.g., pseudouridine (isolated from the yeast t-RNA) and showdomycin (an antibiotic). Development of novel synthetic methodologies allowed the preparation of a large variety of synthetic analogues, which found numerous applications in medicinal chemistry and chemical biology. Most important biologically active C-nucleosides are the inhibitors of purine nucleosides phosphorylase or IMP dehydrogenase. A number of artificial aryl-C-nucleosides capable of π-stacking are being vigorously investigated as building blocks in chemical biology. In the past few years, several Artificial Expanded Genetic Information Systems (AEGIS)1 have been successfully developed as prime examples of synthetic biology, a newly emerging interdisciplinary area, with the ultimate goal to design systems where high-level behaviors of the living matter are mimicked by artificial chemical systems.2,3

C-nucleosides: synthetic strategies and biological applications.

Publisher Summary The C-nucleosides are a group of C-glycosylated heterocycles in which the anomeric carbon atom is attached to the heterocycle by a C-C bond. C-nucleosides have been mainly from fermentation sources, and have been found to exhibit a variety of interesting biological properties. Pyrazomycin has significant antiviral activity. Formycin, formycin B, and oxazinomycins exhibit, in addition, antitumor activity. The biological importance of most of the naturally occurring C-nucleosides has prompted the exploration of synthetic routes leading to these compounds and their analogs. As synthetic targets, the C-nucleosides have deceptively simple structures, and the design of synthetic routes to them must take two important factors into account. Firstly, the methods selected for C-C bond formation at the anomeric center should be stereocontrolled because the structures known thus far are, with two exceptions, β-D-glycosyl compounds. Secondly, the carbon atom attached to the glycosyl group in a C-nucleoside precursor should be appropriately substituted or be amenable to substitution, so as to allow the elaboration of the other heterocyclic portion of the molecule.

Synthesis of naturally occurring C-nucleosides, their analogs, and functionalized C-glycosyl precursors.

A new crystalline antibiotic, minimycin1), C9H11NO7, was isolated from the culture broth of Streptomyces hygroscopicus. Isolation and properties of the new antibiotic are described. Minimycin is active against both Gram-positive and Gram-negative bacteria, and also possesses significant antitumor activity against transplantable tumors.

Minimycin, a new antibiotic

One of the gamones (gamone II) which are effective for the induction of conjugation in Blepharisma intermedium has been isolated in a crystalline form and designated as blepharismin. From the result of chemical and spectroscopic investigations, in which x-ray crystallographic analysis was used as a definitive tool, blepharismin has been found to have the structure of calcium 3-(2'-formylamino-5'-hydroxybenzoyl)lactate.

https://science.sciencemag.org/content/sci/179/4071/400.full.pdf

Yoshiko Tsukuda

Papers

Isolation and Structure Determination of Blepharismin, a Conjugation Initiating Gamone in the Ciliate Blepharisma

Structure of a new class of C-nucleoside antibiotic, showdomycin.