Abstract
Pimaricin (natamycin) is a small polyene macrolide antibiotic used worldwide. This efficient antimycotic and antiprotozoal agent, produced by several soil bacterial species of the genus Streptomyces, has found application in human therapy, in the food and beverage industries and as pesticide. It displays a broad spectrum of activity, targeting ergosterol but bearing a particular mode of action different to other polyene macrolides. The biosynthesis of this only antifungal agent with a GRAS status has been thoroughly studied, which has permitted the manipulation of producers to engineer the biosynthetic gene clusters in order to generate several analogues. Regulation of its production has been largely unveiled, constituting a model for other polyenes and setting the leads for optimizing the production of these valuable compounds. This review describes and discusses the molecular genetics, uses, mode of action, analogue generation, regulation and strategies for increasing pimaricin production yields.
Highlights
Pimaricin (PIM), called natamycin, tennecetin, natacyn and E235, is a natural product produced by given members of the genus Streptomyces, a class of filamentous soil-dwelling bacteria that undergo a complex life cycle involving differentiation and sporulation
Useful reviews about polyene macrolide biosynthesis and analogue generation are available in the literature (Aparicio et al 2003; Aparicio et al 2004; Caffrey et al 2008; Kong et al 2013)
When applied on the surface of foods, it does not affect its organoleptic properties, and has prolonged antimicrobial activity, being safe for consumption because its oral absorption is negligible (Juneja et al 2012). It has been authorised by the European Food Safety Authority (EFSA), the World Health Organisation (WHO) and the Food and Drug Administration (FDA) for protecting foods from yeast and mould contamination and possible inherent risks of mycotoxin poisoning
Summary
Pimaricin (PIM), called natamycin, tennecetin, natacyn and E235, is a natural product produced by given members of the genus Streptomyces, a class of filamentous soil-dwelling bacteria that undergo a complex life cycle involving differentiation and sporulation It belongs to the polyene class of macrolide polyketides, and displays a strong and broad spectrum mould inhibition activity, yet being safe and effective at very low concentrations. Useful reviews about polyene macrolide biosynthesis and analogue generation are available in the literature (Aparicio et al 2003; Aparicio et al 2004; Caffrey et al 2008; Kong et al 2013) This mini-review provides a general view of the applicability of PIM, describes its particular mode of action and highlights the recent advances in the molecular genetics and metabolic engineering of its biosynthetic pathway to produce PIM derivatives with enhanced properties. Appl Microbiol Biotechnol (2016) 100:61–78 provides important insights about the considerable progress attained in recent years aimed to unveil the complex network of regulators involved in its biosynthesis and discusses different strategies for increasing production yields
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