The Use of Baker's Yeast in the Generation of Asymmetric Centers to Produce Chiral Drugs and Other Compounds

Abstract

This review gives a general idea about the importance of chiral carbon in medicine and a way to obtain chiral building blocks with baker's yeast (Saccharomyces cerevisiae) or synthesis of medicaments and other organic compounds. Reactions with these microorganisms are cheaper and easier to be executed than with chemicals (for example, organometallics). Examples of important and practical reactions catalyzed by enzymes inside Saccharomyces cerevisiae are given and probable mechanisms of action of these enzymes are shown. Although these microbes have advantages such as low cost and availability, there are some cares that are necessary to be taken, like NAD(P)H dosage to choose strains more adequate for reduction reactions.

The use of violacein to study biochemical behaviour ofSaccharomyces cerevisiae cells

“…Oxygen consumption was measured with a Clarck-type electrode (Yellow Springs Instruments Co.) in a 1.2 ml thermostated glass chamber equipped with a magnetic stirrer (17,18,21). microorganisms (15,16,18).…”

“…In order to assure that all experiments contained the same number of cells (correction of the stoichiometry), cells were counted using a Neubauer chamber. Glucose was not added to the medium, so it is presumed that the cells were degrading their internal glycogen, which can supply glucose for 10-12h (15,16,21). Glycogen is broken intoglucose-lP, which in turn is broken, via the glycolysispathway, and generates two molecules of ATP and two of NADH.…”

“…In another pathway (pentose phosphate pathway) NADPH molecules are generated (21) All these observations were made having as a goal to study the main biochemical reactions inside eukaryotic cells exposed to violacein. Figure 1 shows measurements of membrane potential (~lJf) which were performed using safranine 0 (an ionochromic indicator), in order to observe if problems were occuring in the integrity of the cell membrane (21). After constructing a base-line, yeast was added at the point indicated in graph (B.Y .…”

“…Safranine 0 is a lipophilic cation and it is nonspecifically absorbed by living cells in response to an electrical gradient, that is, in response to a difference of charge concentration between the extra-and the intracellular medium (membrane potential =~lJf). A TPP+ (tetraphenylphosphonium) electrode was not chosen since this type of electrode can cause some problems when used to measured~lJf in S.cerevisiase (21) To complete this biochemical study, other experiments were performed, as can be seen in Fig. 4 where the oxidation-reduction of cytochrome C (a component of the respiratory chain) is monitored.…”

“…2, a typical control-curve of NAD(P)H production insideintact livingcellsof S. cerevisise is shown(15)(16)(17)(18)21).The control-curve wasmodifiedwhen violacein was added to the medium. The pyridine nucieotides were oxidized in the presence of violacein proportionally to increase of concentration.…”