Polyketide synthase biosynthesis

C. Anthracycline Polyketide Synthases Biosynthesis of Aklanonic Acid... 

Role of polyketide synthases in biosynthesis of some heterocycles, in particular macrolides 97CRV2465. 

The biosynthesis of maduropeptin has not been studied in detail, but an iterative type I polyketide synthase gene predicted to be responsible for forming the enediyne core structure has been identified [188]. 

Kim, J.E. et ah. Putative polyketide synthase and laccase for biosynthesis of auro-fusarin in Gibberella zea, Appl. Environ. Microbiol., 71, 1701, 2005. 

B. Nowak-Thompson, S. J. Gould, and J. E. Loper, Identification and sequence analysis of the genes encoding a polyketide synthase required for pyoluteorin biosynthesis in Pseudomonas fluorescens Pf-5. Gene (1997). 

Shen, B. (2003) Polyketide biosynthesis beyond the type I, II and III polyketide synthase paradigms. Current Opinion in Chemical Biology, 7, 285. 

Kao, C.M., Luo, G.L., Katz, L. et al. (1995) Engineered biosynthesis of a triketide lactone from an incomplete modular polyketide synthase. Journal of the American Chemical Society, 117, 9105. 

The biosynthesis of polyketides (including chain initiation, elongation, and termination processes) is catalyzed by large multi-enzyme complexes called polyketide synthases (PKSs). The polyketides are synthesized from starter units such as acetyl-CoA, propionyl-CoA, and other acyl-CoA units. Extender units such as malonyl-CoA and methylmalonyl-CoA are repetitively added via a decarboxylative process to a growing carbon chain. Ultimately, the polyketide chain is released from the PKS by cleavage of the thioester, usually accompanied by chain cyclization [49]. 

Menzella, H.G., Reid, R., Carney, J.R. et al. (2005) Combinatorial polyketide biosynthesis by de novo design and rearrangement of modular polyketide synthase genes. Nature Biotechnology, 23, 1171-1176. 

Jacobsen, J.R., Hutchinson, C.R., Cane, D.E. and Khosla, C. (1997) Precursor-directed biosynthesis of erythromycin analogs by an engineered polyketide synthase. Science, 277, 367-369. 

Ward, S.L., Desai, R.P., Hu, Z. et al. (2007) Precursor-directed biosynthesis of 6-deoxyerythronolide B analogues is improved by removal of the initial catalytic sites of the polyketide synthase. Journal of Industrial Microbiology and Biotechnology, 34, 9-15. 

Moore, B.S. and Hertweck, C. (2002) Biosynthesis and attachment of novel bacterial polyketide synthase starter units. Natural Product Reports, 19 (1), 70-99. 

STRUCTURALLY GUIDED ALTERATION OF BIOSYNTHESIS IN PLANT TYPE III POLYKETIDE SYNTHASES... 

ABE, I., TAKAHASHI, Y., MORITA, H., NOGUCHI, H., Benzalacetone synthase a novel polyketide synthase that plays a crucial role in the biosynthesis of phenylbutanones in Rheum palmatum, Eur. J. Biochem., 2001,268, 3354-3359. 

The second largest class of compounds reported from macroalgae is the polyketides, which comprise approximately a quarter of known algal compounds (Blunt et al. 2007). Polyketides are polymers of acetate (C2) and occasionally propionate (C3) and are very similar to fatty acids in their biosynthetic origin. Polyketides can be found in plants, animals, bacteria, and fungi. With a range of activities as broad as their structures, the polyketides are a diverse family of natural products classified based upon the polyketide synthases (PKSs) responsible for their biosynthesis, primarily type I and type II. 

Phosphopantetheine tethering is a posttranslational modification that takes place on the active site serine of carrier proteins - acyl carrier proteins (ACPs) and peptidyl carrier proteins (PCPs), also termed thiolation (T) domains - during the biosynthesis of fatty acids (FAs) (use ACPs) (Scheme 23), polyketides (PKs) (use ACPs) (Scheme 24), and nonribosomal peptides (NRPs) (use T domain) (Scheme 25). It is only after the covalent attachment of the 20-A Ppant arm, required for facile transfer of the various building block constituents of the molecules to be formed, that the carrier proteins can interact with the other components of the different multi-modular assembly lines (fatty acid synthases (FASs), polyketide synthases (PKSs), and nonribosomal peptide synthetases (NRPSs)) on which the compounds of interest are assembled. The structural organizations of FASs, PKSs, and NRPSs are analogous and can be divided into three broad classes the types I, II, and III systems. Even though the role of the carrier proteins is the same in all systems, their mode of action differs from one system to another. In the type I systems the carrier proteins usually only interact in cis with domains to which they are physically attached, with the exception of the PPTases and external type II thioesterase (TEII) domains that act in trans. In the type II systems the carrier proteins selectively interact... 

Gaffoor, I., and Trail, F. (2006). Characterization of two polyketide synthase genes involved in zearalenone biosynthesis in Gibberella zeae. Appl. Environ. Microbiol. 72,1793-1799. 

Noel, J.P. et al., Structurally guided alteration of biosynthesis in plant type III polyketide synthases, in Phytochemistry in the Genomics and Post-Genomics Eras, Romeo, J.T. and Dixon, R.A., Eds., Pergamon, New York, 2002, 197. 

Schroder, J., Plant polyketide synthases a chalcone synthase-type enzyme which performs a condensation reaction with methylmalonyl-CoA in the biosynthesis of C-methylated chalcones. 

The biosynthesis of many hydroxylated natural products proceeds through regio- and enantioselective modification of polyketides, which are assembled through chain elongation via acetate or propionate units [2]. The enzymes responsible for the chain elongation and subsequent reduction, elimination, aromatiza-tion, and further modifications are classified as polyketide synthases [3]. These multifunctional enzymes have been used for whole-cell biotransformation toward unnatural metabolites that are within the scope of combinatorial biosynthesis... 

Motivated by the value of these natural products, there has been much research focused on developing guidelines for engineering polyketide synthases to generate natural and novel polyketides [445,446], Additionally, manipulation of the biosynthetic pathways of microbial polyketides through engineering permits the biosynthesis of bioactive polyketides not generated naturally [447,448],... 

Spiteller P, Bai L, Shang G, Carroll BJ, Yu T-W, Floss FIG (2003) The Post-Polyketide Synthase Modification Steps in the Biosynthesis of the Antitumor Agent Ansamitocin by Actinosynnema pretiosum. J Am Chem Soc 125 14236... 

S. L. Ward, Z. Hu, A. Schirmer, R. Reid, W. P. Revill, C. D. Reeves, O. V. Petrakovsky, S. D. Dong, and L. Katz, Chalcomycin biosynthesis gene cluster from Streptomyces bikiniensis Novel features of an unusual ketolide produced through expression of the chm polyketide synthase in Streptomyces fradiae, Antimicrob. Agents Chemother., 48 (2004) 4703-4712 and references therein. 

Keywords Chalcone synthase superfamily enzyme, Engineered biosynthesis, Precursor-directed biosynthesis, Structure-based engineering, Type III polyketide synthase... 

The chalcone synthase (CHS) (EC 2.3.1.74) superfamily of type III Polyketide synthases (PKSs) are pivotal enzymes in the biosynthesis of plant polyphenols. They are structurally and mechanistically different from the modular type I and the dissociated type II PKSs of bacterial origin the simple homodimer of 4CM-5 kDa proteins performs a complete series of decarboxylation, condensation, cyclization,... 

Katsuyama Y, Kita T, Funa N, Horinouchi S (2009) Curcuminoid biosynthesis by two type III polyketide synthases in the herb Curcuma longa. J Biol Chem 284 11160-11170... 

Abe I, Oguro S, Utsumi Y, Sano Y, Noguchi H (2005) Engineered biosynthesis of plant polyketides chain length control in an octaketide-producing plant Type III polyketide synthase. J Am Chem Soc 127 12709-12716... 

Yu T-W, Shen Y, McDaniel R, Floss HG, Khosla C, Hopwood DA, Moore BS (1998) Engineered biosynthesis of novel polyketides from Streptomyces spore pigment polyketide synthases. J Am Chem Soc 120 7749-7759... 

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