Polyene Macrolide Antibiotic Biosynthesis

Aparicio, J. F.; Mendes, M. V.; Antón, N.; Recio, E.; Martín, J. F.
June 2004
Current Medicinal Chemistry;Jun2004, Vol. 11 Issue 12, p1645
Academic Journal
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.


Related Articles

  • Functional specialization in nucleotide sugar transporters occurred through differentiation of the gene cluster EamA (DUF6) before the radiation of Viridiplantae. Västermark, Åke; Almén, Markus Sällman; Simmen, Martin W.; Fredriksson, Robert; Schiöth, Helgi B. // BMC Evolutionary Biology;2011, Vol. 11 Issue 1, p123 

    Background: The drug/metabolite transporter superfamily comprises a diversity of protein domain families with multiple functions including transport of nucleotide sugars. Drug/metabolite transporter domains are contained in both solute carrier families 30, 35 and 39 proteins as well as in...

  • Biochemistry: Enzyme's black box cracked open. Sherman, David H. // Nature;10/22/2009, Vol. 461 Issue 7267, p1068 

    The article focuses on the functionality of polyketide synthase (PKS) enzymes as the biosynthetic machinery that make the molecule to determine the biological activities of polyketides along with other enzymes that adjust polyketide structures to provide additional chemical diversity. It...

  • Acyl carrier protein: structure—function relationships in a conserved multifunctional protein family. Byers, David M.; Huansheng Gong // Biochemistry & Cell Biology;Dec2007, Vol. 85 Issue 6, p649 

    Acyl carrier protein (ACP) is a universal and highly conserved carrier of acyl intermediates during fatty acid synthesis. In yeast and mammals, ACP exists as a separate domain within a large multifunctional fatty acid synthase polyprotein (type I FAS), whereas it is a small monomeric protein in...

  • Enhancing solubility of deoxyxylulose phosphate pathway enzymes for microbial isoprenoid production. Kang Zhou; Ruiyang Zou; Stephanopoulos, Gregory; Heng-Phon Too // Microbial Cell Factories;2012, Vol. 11 Issue 1, p148 

    Background: Recombinant proteins are routinely overexpressed in metabolic engineering. It is well known that some over-expressed heterologous recombinant enzymes are insoluble with little or no enzymatic activity. This study examined the solubility of over-expressed homologous enzymes of the...

  • Incorporation of enzyme concentrations into FBA and identification of optimal metabolic pathways. De, Rajat K.; Das, Mouli; Mukhopadhyay, Subhasis // BMC Systems Biology;2008, Vol. 2, Special section p1 

    Background: In the present article, we propose a method for determining optimal metabolic pathways in terms of the level of concentration of the enzymes catalyzing various reactions in the entire metabolic network. The method, first of all, generates data on reaction fluxes in a pathway based on...

  • Simple Rules Reproduce a Hub-Shaped Cell Metabolic Network. Pfeiffer, T.; Soyer, O. S.; Bonhoeffer, S. // PLoS Biology;Jul2005, Vol. 3 Issue 7, p1153 

    The article presents information related to the study of a cell's metabolic pathways. The researchers employed a computer simulation of a simplified metabolic system to show that two key features in the evolution of a hub system are enzyme specialization and the transfer of chemical groups...

  • Quantitative Analysis of Cellular Metabolic Dissipative, Self-Organized Structures. Martínez de la Fuente, Ildefonso // International Journal of Molecular Sciences;Sep2010, Vol. 11 Issue 9, p3540 

    One of the most important goals of the postgenomic era is understanding the metabolic dynamic processes and the functional structures generated by them. Extensive studies during the last three decades have shown that the dissipative self-organization of the functional enzymatic associations, the...

  • The effect of bio-converted polyunsaturated fatty acids on the oxidation of TAG containing highly unsaturated fatty acids. Young-Mi Kim; Geon-Ho Lee; Young-Geun Yeo; In-Hwan Kim; Kazuo Miyashita; Ching Hou; Sun-Chul Kang; Hak-Ryul Kim // Journal of Industrial Microbiology & Biotechnology;Jan2006, Vol. 33 Issue 1, p17 

    Microbial modification of vegetable fatty acids can often lead to special changes in their structure and in biological function. A bacterial strain, Pseudomonas aeruginosa PR3, is known to carry out multiple hydroxylations on polyunsaturated fatty acids containing 1,4- cis, cis diene structural...

  • Menhaden oil, but not safflower or soybean oil, aids in restoring the polyunsaturated fatty acid profile in the novel delta-6-desaturase null mouse. Monteiro, Jessica; Feng-Jun Li; MacLennan, Mira; Rabalski, Alexandra; Moghadasian, Mohammed H.; Nakamura, Manabu T.; Ma, David W. L. // Lipids in Health & Disease;2012, Vol. 11 Issue 1, p60 

    Background: Polyunsaturated fatty acids (PUFA) have diverse biological effects, from promoting inflammation to preventing cancer and heart disease. Growing evidence suggests that individual PUFA may have independent effects in health and disease. The individual roles of the two essential PUFA,...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics