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.
Keywords: polyene, polyketide synthase, macrolide, antifungal
Current Medicinal Chemistry
Title: Polyene Macrolide Antibiotic Biosynthesis
Volume: 11 Issue: 12
Author(s): J. F. Aparicio, M. V. Mendes, N. Anton, E. Recio and J. F. Martin
Affiliation:
Keywords: polyene, polyketide synthase, macrolide, antifungal
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.
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Cite this article as:
Aparicio F. J., Mendes V. M., Anton N., Recio E. and Martin F. J., Polyene Macrolide Antibiotic Biosynthesis, Current Medicinal Chemistry 2004; 11 (12) . https://dx.doi.org/10.2174/0929867043365044
DOI https://dx.doi.org/10.2174/0929867043365044 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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