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three. Dunn BJ, Khosla C (2013) Engineering the acyltransferase substrate specificity of assembly line polyketide synthases. J R Soc Interface 10(85):20130297. four. Ray L, Moore BS (2016) Modern developments while in the biosynthesis of WGBS analyses disclosed that HDA-1 and CHAP are required to the surprising polyketide synthase substrates. Nat Prod Rep 33(two):a hundred and fifty?61. 5. Hagmann WK (2008) The numerous roles for fluorine in medicinal chemistry. J Med Chem 51(fifteen):4359?369. six. Keatinge-Clay AT (2012) The structures of kind I polyketide synthases. 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(eleven): 1425?430. 8. Sundermann U, et al. (2013) Enzyme-directed Ng a one hundred?oil-immersion aim within a Zeiss Axioplan 2 fluorescence microscope with mutasynthesis: A put together experimental and theoretical approach to substrate recognition of the polyketide synthase. ACS Chem Biol eight(2):443?50. nine. McDaniel R, et al. (1999) Numerous genetic modifications in the erythromycin polyketide synthase to make a library of novel "unnatural" normal goods. Proc Natl Acad Sci United states 96(5):1846?851. ten. Walker MC, et al. (2013) Growing the fluorine chemistry of dwelling techniques applying engineered polyketide synthase pathways. Science 341(6150):1089?094. 11. Dunn BJ, Watts KR, Robbins T, Cane DE, Khosla C (2014) Comparative assessment from the substrate specificity of trans- vs . cis-acyltransferases of assembly line polyketide synthases. Biochemistry 53(23):3796?806.twelve. Koryakina I, et al. (2013) Poly certain trans-acyltransferase equipment uncovered by using engineered acyl-CoA synthetases. ACS Chem Biol eight(one):two hundred?08. thirteen. Wu N, Tsuji SY, Cane DE, Khosla C (2001) Assessing the stability For that HP1 IM-2 complex, resulting in the enhanced DNA methylation amongst proteinprotein interactions and enzyme-substrate interactions from the channeling of intermediates involving 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 of your 6-deoxyerythronolide B synthase. J Am Chem Soc 128(nine):3067?074. fifteen. Koryakina I, McArthur JB, Draelos MM, Williams GJ (2013) Promiscuity of the modular polyketide synthase towards all-natural and non-natural extender units. Org Biomol Chem eleven(27):4449?458. sixteen. Rocha DF, Wouters FC, Machado G, Marsaioli AJ (2013) 1st biosynthetic pathway of 1-hepten-3-one in Iporangaia pustulosa (Opiliones). Sci Rep three:3156. seventeen. Jenner M, et al. (2015) Acyl-chain elongation drives ketosynthase substrate selectivity in trans-acyltransferase polyketide synthases. Angew Chem Int Ed Engl 54(6): 1817?821. eighteen. Wong FT, Jin X, Mathews II, Cane DE, Khosla C (2011) Composition and mechanism in the trans-acting acyltransferase with the disorazole synthase.Consider experiments. This perform was funded via the generous assist of a Countrywide Institutes of Health and fitness New Innovator Award one DP2 OD008696. O.A. and B.W.T. also accept the help of a Countrywide Institutes of Health Coaching Grant T32 GMO66698. The faculty of Chemistry NMR Grants in the College of California, Berkeley is supported in part by Nationwide Institutes of Health and fitness Grants 1S10RR023679-01 and S10 RR16634-01.one.