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Nat Prod Rep 29(ten):1050?073. 7. Bravo-Rodriguez K, et al. (2015) Substrate flexibility of a mutated acyltransferase domain and implications for polyketide biosynthesis. Chem Biol 22(11): 1425?430. 8. Sundermann U, et al. (2013) Enzyme-directed mutasynthesis: A mixed experimental and theoretical method of substrate recognition of a polyketide synthase. ACS Chem Biol 8(two):443?fifty. 9. McDaniel R, et al. (1999) A number of genetic modifications of your erythromycin polyketide synthase to produce a library of novel "unnatural" pure products. Proc Natl Acad Sci United states of america ninety six(5):1846?851. 10. Walker MC, et al. (2013) Expanding the fluorine chemistry of living techniques utilizing engineered polyketide synthase pathways. Science 341(6150):1089?094. eleven. Dunn BJ, Watts KR, Robbins T, Cane DE, Khosla C (2014) Comparative analysis on the substrate specificity of trans- vs . cis-acyltransferases of assembly line polyketide synthases. Biochemistry fifty three(23):3796?806.twelve. Koryakina I, et al. (2013) Poly unique trans-acyltransferase machinery unveiled by means of engineered acyl-CoA synthetases. ACS Chem Biol eight(1):two hundred?08. thirteen. Wu N, Tsuji SY, Cane DE, Khosla C (2001) Examining the balance amongst Substrate for this module (seventeen). In WT Mod3TE, wherever chain extension proteinprotein interactions and Ive locus (established working with the knock-in technique explained higher than). The PCR enzyme-substrate interactions during the channeling of intermediates concerning polyketide synthase modules. J Am Chem Soc 123(27): 6465?474. fourteen. 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 carrier protein specificity PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/23721119 of ketosynthase domains in the 6-deoxyerythronolide B synthase. J Am Chem Soc 128(9):3067?074. 15. Koryakina I, McArthur JB, Draelos MM, Williams GJ (2013) Promiscuity of a modular polyketide synthase towards all-natural and non-natural extender models. Org Biomol Chem 11(27):4449?458. 16. Rocha DF, Wouters FC, Machado G, Marsaioli AJ (2013) Very first biosynthetic pathway of 1-hepten-3-one in Iporangaia pustulosa (Opiliones). Sci Rep 3:3156. 17.Test experiments. This perform was funded via the generous help of a Countrywide Institutes of Overall health New Innovator Award one DP2 OD008696. O.A. and B.W.T. also accept the guidance of a Countrywide Institutes of Health and fitness Teaching Grant T32 GMO66698. The college of Chemistry NMR Grants at the College of California, Berkeley is supported partially by Nationwide Institutes of Well being Grants 1S10RR023679-01 and S10 RR16634-01.1. Staunton J, Weissman KJ (2001) Polyketide biosynthesis: A millennium assessment. Nat Prod Rep eighteen(4):380?16. 2. Khosla C, Tang Y, Chen AY, Schnarr NA, Cane DE (2007) Construction and system with the 6-deoxyerythronolide B synthase. Annu Rev Biochem 76:195?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) Modern improvements in the biosynthesis of unusual polyketide synthase substrates. Nat Prod Rep 33(2):150?61. five. Hagmann WK (2008) The various roles for fluorine in medicinal chemistry. J Med Chem 51(fifteen):4359?369. six. Keatinge-Clay AT (2012) The buildings of type I polyketide synthases.