PMID- 24905764 OWN - NLM STAT- MEDLINE DCOM- 20151214 LR - 20150320 IS - 2161-5063 (Electronic) IS - 2161-5063 (Linking) VI - 4 IP - 3 DP - 2015 Mar 20 TI - Mapping of amino acid substitutions conferring herbicide resistance in wheat glutathione transferase. PG - 221-7 LID - 10.1021/sb500242x [doi] AB - We have used design of experiments (DOE) and systematic variance to efficiently explore glutathione transferase substrate specificities caused by amino acid substitutions. Amino acid substitutions selected using phylogenetic analysis were synthetically combined using a DOE design to create an information-rich set of gene variants, termed infologs. We used machine learning to identify and quantify protein sequence-function relationships against 14 different substrates. The resulting models were quantitative and predictive, serving as a guide for engineering of glutathione transferase activity toward a diverse set of herbicides. Predictive quantitative models like those presented here have broad applicability for bioengineering. FAU - Govindarajan, Sridhar AU - Govindarajan S AD - daggerDNA2.0, Inc., 1140 O'Brien Drive, Suite A, Menlo Park, California 94025, United States. FAU - Mannervik, Bengt AU - Mannervik B AD - double daggerDepartment of Neurochemistry, Stockholm University, SE-10691 Stockholm, Sweden. FAU - Silverman, Joshua A AU - Silverman JA AD - section signCalysta, 1140 O'Brien Drive, Suite B, Menlo Park, California 94025, United States. FAU - Wright, Kathy AU - Wright K AD - daggerDNA2.0, Inc., 1140 O'Brien Drive, Suite A, Menlo Park, California 94025, United States. FAU - Regitsky, Drew AU - Regitsky D AD - section signCalysta, 1140 O'Brien Drive, Suite B, Menlo Park, California 94025, United States. FAU - Hegazy, Usama AU - Hegazy U AD - parallelNational Research Centre, Dokki, Cairo 12311, Egypt. FAU - Purcell, Thomas J AU - Purcell TJ AD - daggerDNA2.0, Inc., 1140 O'Brien Drive, Suite A, Menlo Park, California 94025, United States. FAU - Welch, Mark AU - Welch M AD - daggerDNA2.0, Inc., 1140 O'Brien Drive, Suite A, Menlo Park, California 94025, United States. FAU - Minshull, Jeremy AU - Minshull J AD - daggerDNA2.0, Inc., 1140 O'Brien Drive, Suite A, Menlo Park, California 94025, United States. FAU - Gustafsson, Claes AU - Gustafsson C AD - daggerDNA2.0, Inc., 1140 O'Brien Drive, Suite A, Menlo Park, California 94025, United States. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140613 PL - United States TA - ACS Synth Biol JT - ACS synthetic biology JID - 101575075 RN - 0 (Plant Proteins) RN - EC 2.5.1.18 (Glutathione Transferase) SB - IM MH - Amino Acid Sequence MH - Amino Acid Substitution/*genetics MH - Glutathione Transferase/*chemistry/genetics/metabolism MH - Herbicide Resistance/*genetics MH - Machine Learning MH - Molecular Sequence Data MH - Plant Proteins/*chemistry/genetics/metabolism MH - Research Design MH - Sequence Analysis, Protein MH - Synthetic Biology/*methods MH - Triticum/*genetics OTO - NOTNLM OT - bioengineering OT - design of experiment OT - enzymes OT - herbicide resistance OT - machine learning OT - optimization OT - sequence space OT - synthetic biology EDAT- 2014/06/07 06:00 MHDA- 2015/12/15 06:00 CRDT- 2014/06/07 06:00 PHST- 2014/06/07 06:00 [entrez] PHST- 2014/06/07 06:00 [pubmed] PHST- 2015/12/15 06:00 [medline] AID - 10.1021/sb500242x [doi] PST - ppublish SO - ACS Synth Biol. 2015 Mar 20;4(3):221-7. doi: 10.1021/sb500242x. Epub 2014 Jun 13.