Polyene Macrolide Antibiotic Biosynthesis

Abstract

Polyenes constitute a large class of natural metabolites produced by giant multifunctional enzymes in a process resembling fatty acid biosynthesis. Like fatty acids, polyene macrolides and other polyketides are assembled by decarboxylative condensations of simple carboxylic acids. But while fatty acid intermediates are fully reduced, polyene macrolide intermediates suffer the suppression of reduction or dehydration reactions at given biosynthetic steps. In the last years, much progress has been made in our understanding of the linear and modular organization of the gene clusters, and the enzymes encoded by them, responsible for the biosynthesis of these macrocyclic metabolites. This know-how about the rules that govern polyene chain growth has provided the basis for the first rational manipulations of these fascinating systems for the production of engineered derivatives and promises a new era of novel polyene development, which will hopefully yield new molecules with improved pharmacological properties.

Improvement in aureofuscin production by streptomyces aureofuscus with the addition of acetate and propionate sodium

“…This was attributed to the fact that propionic acid needs to be converted into propionylCoA to act as a precursor for polyene ring synthesis. The enzyme system controlling this step is more active during the exponential growth phase (JING K et al 2011;BIBB MJ 2005;GIL;CAMPELO DIEZ 2003;MARTIN JF;MCDANIEL LE 1976).…”

“…Aureofuscin has the chemical formula C 25 H 37 NO 10 , a molecular mass of 511 (IPRS 1975). Aureofuscin belongs to the polyene antibiotic group and the biosynthesis of the aureofuscin basic chain follows the biosynthesis of fatty acids, which is composed of the decarboxylative condensation of simple carboxylic acids (APARICIO et al 2004). Therefore, the addition of low-molecular weight precursors such as carboxylic acids and amino acids was considered to be an inexpensive, scalable and easy approach to increase the production of different antibiotics, such as in the case of rapamycin (CHENG YR et al 1995), tylosin (NGUYEN et al 1995), pneumocandin (Petersen et al 2001), rampolanin (BRUNATI et al 2005), glycopeptide antibioticA40926 (JOVETIC et al 2008), bitespiramycin (LI ZL et al 2009), and natamycin (ELSAYED et al 2013).…”

Study of Storage Conditions Effect (Light-Heat) on Natamycin Co ntent and Stability in Some Dairy Products (Cheese-Yoghurt)

“…As Safe (GRAS) product by Food and Drug Administration (FDA) [6] and also indicated as a natural preservative by the European Union (EU). Natamycin (Pimaricin) (Figure 1), a polyene macrolide antibiotic, is a potent antifungal compound that can effectively prevent the growth of yeasts and inhibit aflatoxine formation in molds [7]. Natamycin is widely used in the food industry as a natural food preservative for the prevention of mold contamination of beverage, cheese, fruits and other no sterile foods (i.e., cured meats, sausages) [8,9].…”

Glycerol, ethylene glycol and propanediol elicit pimaricin biosynthesis in the PI-factor-defective strain Streptomyces natalensis npi287 and increase polyene production in several wild-type actinomycetes

“…The antibiotic activity of many of these molecules is well known (Berdy, 2005). Many Streptomyces species and some rare actinomycetes have the ability to produce a class of antifungal compounds, the polyene macrolides (Martín, 1977), that belong to the polyketide family (Omura & Tanaka, 1984;Aparicio et al, 2004). In recent years, clusters of genes encoding enzymes for the biosynthesis of a few polyene macrolides have been reported (Aparicio et al, 1999(Aparicio et al, , 2000(Aparicio et al, , 2003Brautaset et al, 2000;Caffrey et al, 2001).…”