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Wu N, Tsuji SY, Cane DE, Khosla C (2001) Evaluating the balance in between proteinprotein interactions and enzyme-substrate interactions in the channeling of Roscovitine Purity & Documentation intermediates concerning polyketide synthase modules. Org Tasocitinib Protocol Biomol Chem 11(27):4449?458. This operate was funded via the generous support of a National Institutes of Wellbeing New Innovator Award one DP2 OD008696. O.A. and B.W.T. also acknowledge the assistance of the Countrywide Institutes of Well being Instruction Grant T32 GMO66698. The college of Chemistry NMR Grants within the College of California, Berkeley is supported partially by Countrywide Institutes of Health and fitness Grants 1S10RR023679-01 and S10 RR16634-01.one. Staunton J, Weissman KJ (2001) Polyketide biosynthesis: A millennium critique. Nat Prod Rep eighteen(4):380?sixteen. two. Khosla C, Tang Y, Chen AY, Schnarr NA, Cane DE (2007) Composition and system with the 6-deoxyerythronolide B synthase. Annu Rev Biochem seventy six:195?21. 3. Dunn BJ, Khosla C (2013) Engineering the acyltransferase substrate specificity of assembly line polyketide synthases. J R Soc Interface ten(85):20130297. 4. Ray L, Moore BS (2016) The latest advancements in the biosynthesis of surprising polyketide synthase substrates. Nat Prod Rep 33(two):a hundred and fifty?61. five. Hagmann WK (2008) The various roles for fluorine in medicinal chemistry. J Med Chem fifty one(fifteen):4359?369. 6. Keatinge-Clay AT (2012) The structures of variety I polyketide synthases. Nat Prod Rep 29(10):1050?073. 7. Bravo-Rodriguez K, et al. (2015) Substrate flexibility of the mutated acyltransferase area and implications for polyketide biosynthesis. Chem Biol 22(11): 1425?430. eight. Sundermann U, et al. (2013) Enzyme-directed mutasynthesis: A put together experimental and theoretical method of substrate recognition of a polyketide synthase. ACS Chem Biol eight(2):443?50. 9. McDaniel R, et al. (1999) Several genetic modifications in the erythromycin polyketide synthase to create a library of novel "unnatural" purely natural products and solutions. Proc Natl Acad Sci Usa 96(five):1846?851. ten. Walker MC, et al. (2013) Increasing the fluorine chemistry of living techniques using engineered polyketide synthase pathways. Science 341(6150):1089?094. 11. Dunn BJ, Watts KR, Robbins T, Cane DE, Khosla C (2014) Comparative investigation with the substrate specificity of trans- as opposed to cis-acyltransferases of assembly line polyketide synthases. Biochemistry 53(23):3796?806.12. Koryakina I, et al. (2013) Poly specific trans-acyltransferase machinery revealed by using engineered acyl-CoA synthetases. ACS Chem Biol eight(one):200?08. thirteen. Wu N, Tsuji SY, Cane DE, Khosla C (2001) Examining the balance between proteinprotein interactions and enzyme-substrate interactions in the channeling of intermediates concerning polyketide synthase modules. J Am Chem Soc 123(27): 6465?474. 14. Chen AY, Schnarr NA, Kim PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/24107419 CY, Cane DE, Khosla C (2006) Extender unit and acyl provider protein specificity PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/23721119 of ketosynthase domains from the 6-deoxyerythronolide B synthase. J Am Chem Soc 128(9):3067?074. fifteen. Koryakina I, McArthur JB, Draelos MM, Williams GJ (2013) Promiscuity of a modular polyketide synthase in the direction of natural and non-natural extender units. Org Biomol Chem 11(27):4449?458. 16.