Gene clusters polyketide

Liu, W., Nonaka, K., Nie, L. et al. (2005) The neocarzinostatin biosynthetic gene cluster from Streptomyces carzinostaticus ATCC 15944 involving two iterative type I polyketide synthases. Chemistry Biology, 12, 293. 

Leadlay, P.F., Staunton, J., Oliynyk, M. et al. (2001) Engineering of complex polyketide biosynthesis — insights from sequencing of the monensin biosynthetic gene cluster. Journal of Industrial Microbiology Biotechnology, 27 (6), 360-367. 

Ikeda, H., Nonomiya, T., Usami, M. et aL (1999) Organization of the biosynthetic gene cluster for the polyketide anthelmintic macrolide avermectin in Streptomyces avermitilis. Proceedings of the National Academy of Sciences of the United States of America, 96, 9509-9514. 

BANGERA, M.G., THOMASHOW, L.S., Identification and characterization of a gene cluster for the synthesis of the polyketide antibiotic 2,4-diacetylphloroglucinol from Pseudomonas fluorescens Q2-87, J. Bacteriol., 1999,181,3155-3163. 

Sudek S, LopanikNB, Waggoner LE, Hildebrand M, Anderson C, Liu HB, Patel A, Sherman DH, Haygood MG (2007) Identification of the putative bryostatin polyketide synthase gene cluster from Candidatus endobugula sertula , the uncultivated microbial symbiont of the marine bryozoan Bugula neritina. J Nat Prod 70 67-74... 

Karolewiez, A., and Geisen, R. (2005). Cloning a part of the ochratoxin A biosynthetic gene cluster of Penicillium nordicum and characterization of the ochratoxin polyketide synthase gene. Syst. Appl. Microbiol. 28, 588-595. 

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. 

Figure 3 Aromatic PKS gene clusters and actinorhodin biosynthesis. Partial gene clusters for the polyketides actinorhodin (act), tetracenomycin (tcm), and doxorubicin (dps) are shown. Reconstitution of combinations of act genes in a PKS clean host have led to a proposed pathway by which the early stages of actinorhodin biosynthesis occur.

Until the biosynthesis of aromatic polyketides can be controlled as precisely as modular PKSs, the most likely utility for this class of PKS is in the generation of libraries to screen for new activities. Due to the highly reactive nature of the aromatic polyketide backbones, a variety of cyclization patterns have been created through combinatorial biosynthesis with aromatic PKS gene clusters... 

Figure 10 Examples of unnatural aromatic polyketides. Libraries of aromatic poly-ketides have been generated using combinations from the actinorhodin, tetracenomycin, frenolicin, griseusin, and whiE spore pigment gene clusters.

T Schweke, JF Aparicio, I Molnar, A Konig, LE Khaw, SF Haydock, M Oliynyk, P Caffrey, J Cortes, JB Lester, G Bohm, J Staunton, PF Leadlay. The biosynthetic gene cluster for the polyketide immunosuppressant rapamycin. Proc Natl Acad Sci... 

C Khosla, S Ebert-Khosla, DA Hopwood. Targeted gene replacements in a Streptomyces polyketide synthase gene cluster role for the acyl carrier protein. Mol Microbiol 6 3237-3249, 1992. 

In addition to those host nonselective toxins, Altemaria pathogens produce a number of host-selective toxins such as AK-toxin, AF-toxin, and ACT-toxin.298 9,10-Epoxy-8-hydroxy-9-methyldecatrienoic acid, the common backbone of these toxins, was biosynthesized via the polyketide pathway. Genetic approach has allowed the identification of a gene cluster for AF-toxin biosynthesis.299... 

Selected examples of other biocatalytic asymmetric oxidations are shown in Figure 20.10. In the area of the polyether ionophore monensin a recently proposed mechanism of oxidative cycUzation of a linear polyketide intermediate by four enzymes, the products of monBI, monBll, monCI, and monCII, has been supported experimentally by analysis of a biosynthetic gene cluster [110] and the accumulation of an B,F,F-triene, when oxidative cydization was blocked [111]. 

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