Accumulation of anE,E,E-Triene by the Monensin-Producing Polyketide Synthase when Oxidative Cyclization is Blocked (original) (raw)
Polyether biosynthesis. 2. Origin of the oxygen atoms of monensin A
Journal of The American Chemical Society, 1982
Feeding of [l-I3C]acetate to cultures of Streptomyces cinnamonensis gave monensin A labeled at carbons 7, 9, 13, 19, and 25, as established by 13C N M R analysis. Similarly, incorporation of [l-13C]propionate resulted in enrichment of carbons 1, 3, 5 , 11, 17, 21, and 23. Further incorporations of [ 1,2-I3C2]acetate, [1,2-13C2]propionate, [2-13C]propionate,
Journal of Industrial Microbiology & Biotechnology, 2001
The biosynthesis of complex reduced polyketides is catalysed in actinomycetes by large multifunctional enzymes, the modular Type I polyketide synthases (PKSs). Most of our current knowledge of such systems stems from the study of a restricted number of macrolide-synthesising enzymes. The sequencing of the genes for the biosynthesis of monensin A, a typical polyether ionophore polyketide, provided the first genetic evidence for the mechanism of oxidative cyclisation through which polyethers such as monensin are formed from the uncyclised products of the PKS. Two intriguing genes associated with the monensin PKS cluster code for proteins, which show strong homology with enzymes that trigger double bond migrations in steroid biosynthesis by generation of an extended enolate of an unsaturated ketone residue. A similar mechanism operating at the stage of an enoyl ester intermediate during chain extension on a PKS could allow isomerisation of an E double bond to the Z isomer. This process, together with epoxidations and cyclisations, form the basis of a revised proposal for monensin formation. The monensin PKS has also provided fresh insight into general features of catalysis by modular PKSs, in particular into the mechanism of chain initiation. Journal of Industrial Microbiology & Biotechnology (2001) 27, 360–367.
Evidence for the Role of the monB Genes in Polyether Ring Formation during Monensin Biosynthesis
Chemistry & Biology, 2006
Ionophoric polyethers are produced by the exquisitely stereoselective oxidative cyclization of a linear polyketide, probably via a triepoxide intermediate. We report here that deletion of either or both of the monBI and monBII genes from the monensin biosynthetic gene cluster gave strains that produced, in place of monensins A and B, a mixture of C-3-demethylmonensins and a number of minor components, including C-9-epimonensin A. All the minor components were efficiently converted into monensins by subsequent acid treatment. These data strongly suggest that epoxide ring opening and concomitant polyether ring formation are catalyzed by the MonB enzymes, rather than by the enzyme MonCII as previously thought. Consistent with this, homology modeling shows that the structure of MonB-type enzymes closely resembles the recently determined structure of limonene-1,2-epoxide hydrolase from Rhodococcus erythropolis.
ChemInform Abstract: Biosynthesis of Polyketide Synthase Extender Units
ChemInform, 2009
The biosynthetic pathways to polyketide-derived polycyclic ethers, in bacteria, plants and marine organisms, have, until now, tended to be considered separately. The purpose of this article is to provide an integrated review of the common mechanistic aspects of polyether biosynthesis from these diverse sources. In particular, the focus will be on the proposed mechanisms of oxidative cyclisation, as well as on the known differences in polyketide chain construction between the terrestrial and marine polyethers.
ChemInform Abstract: The Biosynthesis of Polyketide-Derived Polycyclic Ethers
ChemInform, 2009
The biosynthetic pathways to polyketide-derived polycyclic ethers, in bacteria, plants and marine organisms, have, until now, tended to be considered separately. The purpose of this article is to provide an integrated review of the common mechanistic aspects of polyether biosynthesis from these diverse sources. In particular, the focus will be on the proposed mechanisms of oxidative cyclisation, as well as on the known differences in polyketide chain construction between the terrestrial and marine polyethers.
The biosynthesis of polyketide-derived polycyclic ethers
Natural Product Reports, 2009
The biosynthetic pathways to polyketide-derived polycyclic ethers, in bacteria, plants and marine organisms, have, until now, tended to be considered separately. The purpose of this article is to provide an integrated review of the common mechanistic aspects of polyether biosynthesis from these diverse sources. In particular, the focus will be on the proposed mechanisms of oxidative cyclisation, as well as on the known differences in polyketide chain construction between the terrestrial and marine polyethers.
A Polyketide Synthase Component for Oxygen Insertion into Polyketide Backbones
Angewandte Chemie International Edition
Enzymatic core components from trans-acyltransferase polyketide synthases (trans-ATP KSs) catalyze exceptionally diverse biosynthetic transformations to generate structurally complex bioactive compounds.H ere we focus on ag roup of oxygenases identified in various trans-ATP KS pathways, including those for pederin, oocydins,and toblerols. Using the oocydin pathway homologue (OocK) from Serratia plymuthica 4Rx13 and N-acetylcysteamine (SNAC)t hioesters as test surrogates for acyl carrier protein (ACP)-tethered intermediates,w es howt hat the enzyme inserts oxygen into bketoacyl moieties to yield malonyl ester SNAC products.Based on these data and the identification of an on-hydrolyzed oocydin congener with retained ester moiety,w ep ropose aunified biosynthetic pathwayofoocydins,haterumalides,and biselides.B yp roviding access to internal ester,c arboxylate pseudostarter,a nd terminal hydroxylf unctions,o xygen insertion into polyketide backbones greatly expands the biosynthetic scope of PKSs.