High-throughput screening for terpene-synthase-cyclization activity and directed evolution of a terpene synthase.

The development of high-throughput assays can be extremely challenging, yet is essential for many applications in drug discovery and enzyme engineering.

[1]  Y. Lee,et al.  A rapid formaldehyde assay using purpald reagent: application under periodation conditions. , 1996, Analytical biochemistry.

[2]  J. Noel,et al.  Interception of the Enzymatic Conversion of Farnesyl Diphosphate to 5‐Epi‐Aristolochene by Using a Fluoro Substrate Analogue: 1‐Fluorogermacrene A from (2E,6Z)‐6‐Fluorofarnesyl Diphosphate , 2007, Chembiochem : a European journal of chemical biology.

[3]  J. Keasling,et al.  Engineering Cotton (+)-δ-Cadinene Synthase to an Altered Function: Germacrene D-4-ol Synthase , 2006 .

[4]  D. Cane,et al.  Structural and mechanistic analysis of trichodiene synthase using site-directed mutagenesis: probing the catalytic function of tyrosine-295 and the asparagine-225/serine-229/glutamate-233-Mg2+B motif. , 2008, Archives of biochemistry and biophysics.

[5]  Andreas Vogel,et al.  Iterative saturation mutagenesis on the basis of B factors as a strategy for increasing protein thermostability. , 2006, Angewandte Chemie.

[6]  E. Csöregi,et al.  Photometric assay of methanol and formaldehyde in industrial waste-waters using alcohol oxidase and 3-methyl-2-benzothiazolinone hydrazone , 2008 .

[7]  Thomas E. Ferrin,et al.  Designed divergent evolution of enzyme function , 2006, Nature.

[8]  Jonathan Bronson,et al.  Computational design and selections for an engineered, thermostable terpene synthase , 2011, Protein science : a publication of the Protein Society.

[9]  H. Chiu,et al.  Trichodiene Synthase: Synthesis and Inhibition Kinetics of 12‐Fluoro‐farnesylphosphonophosphate for Sesquiterpene Cyclases , 2006 .

[10]  B. Nestl,et al.  Stereoselective Friedel–Crafts alkylation catalyzed by squalene hopene cyclases , 2012 .

[11]  M. Komatsu,et al.  Genome mining in Streptomyces avermitilis: cloning and characterization of SAV_76, the synthase for a new sesquiterpene, avermitilol. , 2010, Journal of the American Chemical Society.

[12]  R. Peters,et al.  Terpenoid synthase structures: a so far incomplete view of complex catalysis. , 2012, Natural product reports.

[13]  C. Schmidt-Dannert,et al.  Identification of Sesquiterpene Synthases from Nostoc punctiforme PCC 73102 and Nostoc sp. Strain PCC 7120 , 2008, Journal of bacteriology.

[14]  Kelly M. Thayer,et al.  Combining metabolic and protein engineering of a terpenoid biosynthetic pathway for overproduction and selectivity control , 2010, Proceedings of the National Academy of Sciences.

[15]  D. Cane,et al.  Expression and mechanistic analysis of a germacradienol synthase from Streptomyces coelicolor implicated in geosmin biosynthesis , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[16]  T. Köllner,et al.  A multiproduct terpene synthase from Medicago truncatula generates cadalane sesquiterpenes via two different mechanisms. , 2010, The Journal of organic chemistry.

[17]  J. Noel,et al.  Quantitative exploration of the catalytic landscape separating divergent plant sesquiterpene synthases , 2008, Nature chemical biology.

[18]  C. Schmidt-Dannert,et al.  Diversity of sesquiterpene synthases in the basidiomycete Coprinus cinereus , 2009, Molecular microbiology.

[19]  D. Barrett,et al.  Comparison of three colorimetric reagents in the determination of methanol with alcohol oxidase. Application to the assay of pectin methylesterase. , 2004, Journal of agricultural and food chemistry.

[20]  D. Cane,et al.  Genome mining in Streptomyces clavuligerus: expression and biochemical characterization of two new cryptic sesquiterpene synthases. , 2011, Chemistry & biology.

[21]  Keith E. J. Tyo,et al.  Isoprenoid Pathway Optimization for Taxol Precursor Overproduction in Escherichia coli , 2010, Science.

[22]  D. Cane,et al.  Genome mining in Streptomyces coelicolor: molecular cloning and characterization of a new sesquiterpene synthase. , 2006, Journal of the American Chemical Society.

[23]  David J. Miller,et al.  Aristolochene Synthase‐Catalyzed Cyclization of 2‐Fluorofarnesyl‐Diphosphate to 2‐Fluorogermacrene A , 2007, Chembiochem : a European journal of chemical biology.

[24]  D. Cane,et al.  Sesquiterpene synthase from the botrydial biosynthetic gene cluster of the phytopathogen Botrytis cinerea. , 2008, ACS chemical biology.

[25]  D. Christianson.  Unearthing the roots of the terpenome. , 2008, Current opinion in chemical biology.

[26]  E. Corey,et al.  An experimental demonstration of the stereochemistry of enzymic cyclization of 2,3-oxidosqualene to the protosterol system, forerunner of lanosterol and cholesterol , 1991 .

[27]  Paul A Dalby,et al.  Strategy and success for the directed evolution of enzymes. , 2011, Current opinion in structural biology.

[28]  Manfred T. Reetz,et al.  Enhancing the Thermal Robustness of an Enzyme by Directed Evolution: Least Favorable Starting Points and Inferior Mutants Can Map Superior Evolutionary Pathways , 2011, Chembiochem : a European journal of chemical biology.

[29]  Philip A. Romero,et al.  Exploring protein fitness landscapes by directed evolution , 2009, Nature Reviews Molecular Cell Biology.

[30]  R. Coates,et al.  Synthesis of Methoxynor Polyisoprenoid Alcohols by Alkylation of (3-Methoxyallyl)lithium Reagents , 2002 .

[31]  J. A. Klavons,et al.  Determination of methanol using alcohol oxidase and its application to methyl ester content of pectins , 1986 .

[32]  David J. Miller,et al.  6- and 14-Fluoro farnesyl diphosphate: mechanistic probes for the reaction catalysed by aristolochene synthase. , 2009, Organic & biomolecular chemistry.

[33]  J. Noel,et al.  Identifying and manipulating structural determinates linking catalytic specificities in terpene synthases. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[34]  Jürgen Pleiss,et al.  Activation-Independent Cyclization of Monoterpenoids , 2011, Applied and Environmental Microbiology.

[35]  P M Dewick.  The biosynthesis of C5-C25 terpenoid compounds. , 1997, Natural product reports.

[36]  W. Setzer.  Ab initio analysis of the Cope rearrangement of germacrane sesquiterpenoids , 2008, Journal of molecular modeling.

[37]  H. Bouwmeester,et al.  (+)-Germacrene A biosynthesis . The committed step in the biosynthesis of bitter sesquiterpene lactones in chicory , 1998, Plant physiology.

[38]  C. Poulter,et al.  Farnesyl diphosphate analogues with omega-bioorthogonal azide and alkyne functional groups for protein farnesyl transferase-catalyzed ligation reactions. , 2007, The Journal of organic chemistry.

[39]  David J. Miller,et al.  Chemoenzymatic preparation of germacrene analogues. , 2012, Chemical communications.

[40]  Shuiqin Wu,et al.  Conformational Analysis of (+)-Germacrene A by Variable Temperature NMR and NOE Spectroscopy. , 2007, Tetrahedron.

[41]  Dan S. Tawfik,et al.  Directed enzyme evolution: beyond the low-hanging fruit. , 2012, Current opinion in structural biology.