Comparative Study of a Semisynthetic Derivative of Natamycin and the Parent Antibiotic on the Spoilage of Shredded Cheddar Cheese

Abstract

The polyene macrolide antibiotic natamycin (Antibiotic A-5283) is commonly used to retard the growth of surface molds on various cheese varieties. Natamycin is commonly applied to the surface of cheese by dipping or spraying, using an aqueous dispersion containing 200 to 300 ppm of the additive. The large molecular weight of natamycin, 666 g/mol, and conjugated double bond structure causes it to be extremely insoluble in water and most food grade solvents. The inability to apply natamycin in true solution creates void non-treated areas on the food surface. These non-treated areas promote the growth of fungal organisms.A water soluble N-alkyl semisynthetic derivative of natamycin was synthesized by the Michael addition reaction of the parent with a N-substituted malemide. A comparative study investigating the effectiveness of the semisynthetic derivative of natamycin and the parent antibiotic in suppressing mold growth on one month aged shredded Cheddar cheese modified atmosphere packaged (MAP) was performed. A 20 ppm natamycin treatment effectively suppressed visible mold growth (<10 4 CFU/g) in MAP samples for up to 30 days after opening. The 20 ppm semisynthetic derivative performed similarly to the 10 ppm natamycin treatment in retarding mold growth. Visible mold growth did not occur for these treatments in MAP samples until 20 days after opening. Analysis of storage conditions revealed that an outgrowth of mold in shredded cheese occurred in MAP packages stored longer than 15 days. This bloom in mold growth was attributed to the degradation of natamycin and the semisynthetic derivative throughout storage.The stability and degradation of natamycin and the derivative were monitored throughout the study. Antibiotic concentration on the cheese surface was quantified by molecular absorption spectrometry. Results from this study showed, heavily contaminated samples caused the rate and loss of natamycin and the derivative to increase. Antibiotic concentration decreased at a similar rate in MAP and open package conditions. Natamycin and derivative were found to have similar degradation properties.iii DEDICATION This thesis is dedicated to my wife, Amy Lynn Suloff. I cannot express in words the love and support Amy provided during this project. For these endearing qualities, and so many more I want to thank her. iv ACKNOWLEDGMENTS

Biotechnological production and application of the antibiotic pimaricin: biosynthesis and its regulation

“…In the search for improvement of PIM properties, a good number of semi-synthetic derivatives have been described in the literature, including esters (Bonner et al 1972 ; Falkowski et al 1979 ), N,N-dialkyl (Paquet and Carreira 2006 ), N-alkyl (Suloff et al 2003 ), N-acyl (Nirgudkar et al 1988 ), N-glycosil (Falkowski et al 1980 ), N-aryl (Belakhov et al 2010 ) and hydrophosphoryl derivatives (Belakhov et al 2008 ), amongst others. Liposomal preparations have been also studied (Bouaoud et al 2015 ).…”

Challenge of Drug Solubility Prediction

“…A quick internet search yields values ranging from − 2.1 to − 4.1. More importantly, Suloff [48] reports it to be a zwitterion in water, which is quite plausible. Hence it is almost impossible to predict such high solubility from the neutral structure given in the Huuskonen dataset.…”

Semisynthetic Amides of Polyene Antibiotic Natamycin

“…Hence, such simple modifications of the natamycin core are a promising way to obtain new water-soluble polyene antifungals with low toxicity. Until now, only few natamycin derivatives have been described, such as those created by the gene engineering of producing microorganisms 18,19 and two semisynthetic derivatives, synthesized by the Michael addition reaction of the parent antibiotic with an N-substituted malemide 20 and by Oalkylation of the C12-carboxylic group with diazomethane. 21 Also, a naturally occurring natamycin analog, an amide named AB-400 was described.…”