Engineering biosynthesis

Kato, Y., Bai, L., Xue, Q. et al. (2002) Functional expression of genes involved in the biosynthesis of the novel polyketide chain extension unit, methoxymalonyl-acyl carrier protein, and engineered biosynthesis of 2-desmethyl-2-methoxy-6-deoxyerythronolide B. Journal of the American Chemical Society, 124, 5268. 

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. 

Hojati, Z., Milne, C., Harvey B. et al. (2002) Structure, biosynthetic origin, and engineered biosynthesis of calcium-dependent antibiotics from Streptomyces coelicolor. Chemistry Biology, 9, 1175. 

Fig. 3 Metabolic routes towards biopolyester synthesis. Dashed lines represent engineered biosynthesis routes. Triangles depict targets for inhibitors enabling biopolyester synthesis. Enzymes indicated on shaded boxes on solid lines are biopolyester biosynthesis enzymes. With kind permission from Springer Science+Business Media [7]...

Engineered Biosynthesis of Plant Polyketides Structure-Based and Precursor-Directed Approach... 

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

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... 

Fu H, Ebert-Khosla S, Hopwood DA, Khosla C (1994) Engineered biosynthesis of novel polyketides dissection of the catalytic specificity of the act ketoreductase. J Am Chem Soc 116 4166-4170... 

Abe I, Watanabe T, Morita H, Kohno T, Noguchi H (2006) Engineered biosynthesis of plant polyketides manipulation of chalcone synthase. Org Lett 8 499-502... 

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... 

Melancon CE IB, Liu HW (2007) Engineered biosynthesis of macrolide derivatives bearing the non-natural deoxysugars 4-epi-D-mycaminose and 3-N-methylamino-3-deoxy-D-fucose. J Am Chem Soc 129 4896 1899... 

Gaisser S, Martin CJ, Wilkinson B et al (2002) Engineered biosynthesis of novel spinosyns bearing altered deoxyhexose substituents. Chem Commun 21 618-619... 

Schell U, Haydock SF, Kaja AL et al (2008) Engineered biosynthesis of hybrid macrolide polyketides containing D-angolosamine and D-mycaminose moieties. Org Biomol Chem 6 3315-3327... 

The discovery of PKSs has led to the emergence of new horizons for the engineered biosynthesis of complex natural product-like molecules. The goals of this chapter are twofold. First, we will summarize our understanding of these systems at a molecular level, and the techniques that have emerged to dissect and manipulate these systems. Second, we will present selected examples of how PKSs can be engineered to synthesize novel biomolecules, and the pharmacological implications of such manipulation. Hopefully it will become clear that, al-... 

R McDaniel, S Ebert-Khosla, DA Hopwood, C Khosla. Engineered biosynthesis of novel polyketides. Science 262 1546-1550, 1993. 

CM Kao, L Katz, C Khosla. Engineered biosynthesis of a complete macrolactone in a heterologous host. Science 265 509-512, 1994. 

CM Kao, M McPherson, RN McDaniel, HFu, DE Cane, C Khosla. Gain of function mutagenesis of a modular polyketide synthase II. Engineered biosynthesis of an eight-membered ring tetraketide lactone. J Am Chem Soc 119 11339-11340,... 

PJ Kramer, RJX Zawada, R McDaniel, CR Hutchinson, DA Hopwood, C Khosla. Rational design and engineered biosynthesis of a novel 18-carbon aromatic polyketide. J Am Chem Soc 119 635-639, 1997. 

Gaisser S, Martin CJ, WiUdnson B, Sheridan RM, Lill RE, Weston AJ, Ready SJ, Waldron C, Crouse GD, Leadlay PE, Staunton J (2002) Engineered Biosynthesis of Novel Spinosyns Bearing Altered Deoxyhexose Substituents. Chem Commun 618... 

Schell U, Haydock SF, Kaja AL, Carletti I, Lill RE, Read E, Sheehan LS, Low L, Fernandez MJ, Grolle F, McArthur HA, Sheridan RM, Leadlay PF, Wilkinson B, Gaisser S (2008) Engineered Biosynthesis of Hybrid Macrolide Polyketides Containing D-Angolosamine and D-Mycaminose Moieties. Org Biomol Chem 6 3315... 

The power of combinatorial biosynthesis has been best demonstrated through the engineered biosynthesis of polyketides." Polyketides consist of a structurally diverse family of natural products and are mostly biosynthesized by soil-bome actinomyces as secondary metabolites. Fungi and plants have also been sources of polyketides. 

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