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Molecular Basis for Polyketide Ketoreductase–Substrate Interactions.

Zhao S, Ni F,  Qiu T,  Wolff JT,  Tsai SC,  Luo R.

Int. J. Mol. Sci. 2020, 21, 7562.

Structural basis for chain release from the enacyloxin polyketide synthase.
Kosol S, Gallo A, Griffiths D, Valentic TR, Masschelein J, Jenner M, de Los Santos ELC, Manzi L, Sydor PK, Rea D, Zhou S, Fülöp V, Oldham NJ, Tsai SC, Challis GL, Lewandowski JR.

Nat Chem. 2019 Oct;11(10):913-923.

Molecular basis for interactions between an acyl carrier protein and a ketosynthase.
Milligan JC, Lee DJ, Jackson DR, Schaub AJ, Beld J, Barajas JF, Hale JJ, Luo R, Burkart MD, Tsai SC.

Nat Chem Biol. 2019 Jul;15(7):669-671. 

Computational structural enzymology methodologies for the study and engineering of fatty acid synthases, polyketide synthases and nonribosomal peptide synthetases.
Schaub AJ, Moreno GO, Zhao S, Truong HV, Luo R, Tsai SC.

Methods Enzymol. 2019;622:375-409.

The Structural Enzymology of Iterative Aromatic Polyketide Synthases: A Critical Comparison with Fatty Acid Synthases.
Tsai SC

Annu Rev Biochem. 2018 Jun 20;87:503-531. 

An Oxetane-Based Polyketide Surrogate To Probe Substrate Binding in a Polyketide Synthase.

Ellis BD, Milligan JC, White AR, Duong V, Altman PX, Mohammed LY, Crump MP, Crosby J, Luo R, Vanderwal CD, Tsai SC.

J Am Chem Soc. 2018 Apr 18;140(15):4961-4964.

Structural and Functional Studies of the Daunorubicin Priming Ketosynthase DpsC.

Jackson DR, Shakya G, Patel AB, Mohammed LY, Vasilakis K, Wattana-Amorn P, Valentic TR, Milligan JC, Crump MP, Crosby J, Tsai SC.

ACS Chem Biol. 2018 Jan 19;13(1):141-151

A Direct Synthesis of Highly Substituted π-Rich Aromatic Heterocycles from Oxetanes.

White AR, Kozlowski RA, Tsai SC, Vanderwal CD.

Angew Chem Int Ed Engl. 2017 Aug 21;56(35):10525-10529

Polyketide mimetics yield structural and mechanistic insights into product template domain function in nonreducing polyketide synthases

Barajas JF, Shakya G, Moreno G, Rivera H Jr, Jackson DR, Topper CL, Vagstad AL, La Clair JJ, Townsend CA, Burkart MD, Tsai SC

Proc Natl Acad Sci U S A. 2017 May 23;114(21):E4142-E4148

A crotonyl-CoA reductase-carboxylase independent pathway for assembly of unusual alkylmalonyl-CoA polyketide synthase extender units

Ray L, Valentic TR, Miyazawa T, Withall DM, Song L, Milligan JC, Osada H, Takahashi S, Tsai SC, Challis GL

Nat Commun. 2016 Dec 21;7:13609

Comprehensive Analysis of a Novel Ketoreductase for Pentangular Polyphenol Biosynthesis

Valentic TR, Jackson DR, Brady SF, Tsai SC

ACS Chem Biol. 2016 Dec 16;11(12):3421-3430


Structural and Biochemical Analysis of Protein-Protein Interactions Between the Acyl-Carrier Protein and Product Template Domain

Barajas JF, Finzel K, Valentic TR, Shakya G, Gamarra N, Martinez D, Meier JL, Vagstad AL, Newman AG, Townsend CA, Burkart MD, Tsai SC

Angew Chem Int Ed Engl. 2016 Oct 10;55(42):13005-13009


An unusual intramolecular trans-amidation

Rivera H Jr, Dhar S, La Clair JJ, Tsai SC, Burkart MD

Tetrahedron. 2016 Jun 23;72(25):3605-3608


The Alga Ochromonas danica Produces Bromosulfolipids

White AR, Duggan BM, Tsai SC, Vanderwal CD

Org Lett. 2016 Mar 4;18(5):1124-7


Insights Into Complex Oxidation During BE-7585A Biosynthesis: Structural Determination and Analysis of the Polyketide Monooxygenase BexE

Jackson DR, Yu X, Wang G, Patel AB, Barajas JF, Sasaki E, Metsa-Ketala M, Liu HW, Rohr J, Tsai SC

ACS Chem Biol. 2016 Apr 15;11(4):1137-47

Structural Insights Into Anthranilate Priming During Type II Polyketide Biosynthesis

Jackson D, Tu SS, Nguyen M, Barajas J, Schaub A, Krug D, Pistorius D, Luo R, Müller R, Tsai SC

ACS Chem Biol. 2016 Jan 15;11(1):95-103


Structural and functional analysis of two di-domain aromatase/cyclases from type II polyketide synthases

Caldara-Festin G, Jackson DR, Barajas JF, Valentic TR, Patel AB, Aguilar S, Nguyen M, Vo M, Khanna A, Sasaki E, Liu H, Tsai SC

Proc Natl Acad Sci U S A. 2015 Dec 15;112(50):E6844-51


Probing the Substrate Specificity and Protein-Protein Interactions of the E. coli Fatty Acid Dehydratase, FabA

Finzel K, Nguyen C, Jackson DR, Gupta A, Tsai SC, Burkart MD

Chem Biol. 2015 Nov 19;22(11):1453-60


Comprehensive Structural and Biochemical Analysis of the Terminal Myxalamid Reductase Domain for the Engineered Production of Primary Alcohols

Barajas JF, Phelan RM, Schaub AJ, Kliewer JT, Kelly PJ, Jackson DR, Luo R, Keasling JD, Tsai SC

Chem Biol. 2015 Aug 20;22(8):1018-29


Modeling linear and cyclic PKS intermediates through Atom Replacement

Shakya G, Rivera H Jr, Lee DJ, Jaremko MJ, La Clair JJ, Fox DT, Haushalter RW, Schaub AJ, Bruegger J, Barajas JF, White AR, Kaur P, Gwozdziowski ER, Wong F, Tsai SC, Burkart MD

J Am Chem Soc. 2014 Dec 3;136(48):16792-9


Editorial: fungal natural products themed issue

Challis GL, Tsai SC

Nat Prod Rep. 2014 Oct;31(10):1241

Polyketide Synthase: Sequence, Structure, and Function

Bruegger J, Caldara G, Beld J, Burkart MD, Tsai SC

Natural Products: Discourse, Diversity, and Design, 219. 2014


Trapping the dynamic acyl carrier protein in fatty acid biosynthesis

Nguyen C, Haushalter RW, Lee DJ, Markwick PR, Bruegger J, Caldara-Festin G, Finzel K, Jackson DR, Ishikawa F, O'Dowd B, McCammon JA, Opella SJ, Tsai SC, Burkart MD

Nature. 2014 Jan 16;505(7483):427-31


The determinants of activity and specificity in actinorhodin type II polyketide ketoreductase

Javidpour P, Bruegger J, Srithahan S, Korman TP, Crump MP, Crosby J, Burkart MD, Tsai SC

Chem Biol. 2013 Oct 24;20(10):1225-34


Probing the selectivity and protein·protein interactions of a nonreducing fungal polyketide synthase using mechanism-based crosslinkers

Bruegger J, Haushalter RW, Vagstad AL, Shakya G, Mih N, Townsend CA, Burkart MD, Tsai SC

Chem Biol. 2013 Sep 19;20(9):1135-46


Editorial: structural aspects of biosynthesis themed issue

Tsai SC, Moore B, O'Connor S

Nat Prod Rep. 2012 Oct;29(10):1032


Babysitting flavin for biosynthesis

Tsai SC

Chem Biol. 2012 Jul 27;19(7):787-8


Crystal structure and biochemical studies of the trans-acting polyketide enoyl reductase LovC from lovastatin biosynthesis

Ames BD, Nguyen C, Bruegger J, Smith P, Xu W, Ma S, Wong E, Wong S, Xie X, Li JW, Vederas JC, Tang Y, Tsai SC

Proc Natl Acad Sci U S A. 2012 Jul 10;109(28):11144-9


Insight into the molecular basis of aromatic polyketide cyclization: crystal structure and in vitro characterization of WhiE-ORFVI

Lee MY, Ames BD, Tsai SC

Biochemistry. 2012 Apr 10;51(14):3079-91


Structural and biochemical characterization of ZhuI aromatase/cyclase from the R1128 polyketide pathway

Ames BD, Lee MY, Moody C, Zhang W, Tang Y, Tsai SC

Biochemistry. 2011 Oct 4;50(39):8392-406


Structural and biochemical studies of the hedamycin type II polyketide ketoreductase (HedKR): molecular basis of stereo- and regiospecificities

Javidpour P, Das A, Khosla C, Tsai SC

Biochemistry. 2011 Aug 30;50(34):7426-39


Structural and biochemical analyses of regio- and stereospecificities observed in a type II polyketide ketoreductase

Javidpour P, Korman TP, Shakya G, Tsai SC

Biochemistry. 2011 May 31;50(21):4638-49


Fatty acid biosynthesis in actinomycetes

Gago G, Diacovich L, Arabolaza A, Tsai SC, Gramajo H

FEMS Microbiol Rev. 2011 May;35(3):475-97


Crystal structures and mutational analyses of acyl-CoA carboxylase beta subunit of Streptomyces coelicolor

Arabolaza A, Shillito ME, Lin TW, Diacovich L, Melgar M, Pham H, Amick D, Gramajo H, Tsai SC

Biochemistry. 2010 Aug 31;49(34):7367-76


X-ray crystallographic structure of an artificial beta-sheet dimer

Khakshoor O, Lin AJ, Korman TP, Sawaya MR, Tsai SC, Eisenberg D, Nowick JS

J Am Chem Soc. 2010 Aug 25;132(33):11622-8


Structure and function of an iterative polyketide synthase thioesterase domain catalyzing Claisen cyclization in aflatoxin biosynthesis

Korman TP, Crawford JM, Labonte JW, Newman AG, Wong J, Townsend CA, Tsai SC

Proc Natl Acad Sci U S A. 2010 Apr 6;107(14):6246-51


Structural basis for biosynthetic programming of fungal aromatic polyketide cyclization

Crawford JM, Korman TP, Labonte JW, Vagstad AL, Hill EA, Kamari-Bidkorpeh O, Tsai SC, Townsend CA

Nature. 2009 Oct 22;461(7267):1139-43


ACCase 6 is the essential acetyl-CoA carboxylase involved in fatty acid and mycolic acid biosynthesis in mycobacteria

Kurth DG, Gago GM, de la Iglesia A, Bazet Lyonnet B, Lin TW, Morbidoni HR, Tsai SC, Gramajo H

Microbiology. 2009 Aug;155(Pt 8):2664-75


Structural enzymology of polyketide synthases

Tsai SC, Ames BD

Methods Enzymol. 2009;459:17-47


Structural enzymology of type II polyketide synthase: the structure-sequence-function correlation"

Korman TP, Ames BD, Tsai SC

"Comprehensive Natural Products", 2009, Elsevier Press


2.6 Å X-ray crystal structure of human p53R2, a p53 inducible ribonucleotide reductase

Smith P, Zhou, BZ, Ho N, Yuan YC, Su L, Tsai SC, Yen Y

Biochemistry, 2009, 48, 11134


Crystal structure and functional analysis of tetracenomycin ARO/CYC: implications for cyclization specificity of aromatic polyketides

Ames BD, Korman TP, Zhang W, Smith P, Vu T, Tang Y, Tsai SC

Proc Natl Acad Sci U S A. 2008 Apr 8;105(14):5349-54


Inhibition kinetics and emodin cocrystal structure of a type II polyketide ketoreductase

Korman TP, Tan YH, Wong J, Luo R, Tsai SC

Biochemistry. 2008 Feb 19;47(7):1837-47


The type I fatty acid and polyketide synthases: a tale of two megasynthases

Smith S, Tsai SC

Nat Prod Rep. 2007 Oct;24(5):1041-72


Engineered biosynthesis of a novel amidated polyketide, using the malonamyl-specific initiation module from the oxytetracycline polyketide synthase

Zhang W, Ames BD, Tsai SC, Tang Y

Appl Environ Microbiol. 2006 Apr;72(4):2573-80


Biosynthesis of a 3,6-dideoxyhexose: crystallization and X-ray diffraction of CDP-6-deoxy-L-threo-D-glycero-4-hexulose-3-dehydrase (E1) for ascarylose biosynthesis

Smith P, Lin A, Szu PH, Liu HW, Tsai SC

Acta Crystallogr Sect F Struct Biol Cryst Commun. 2006 Mar 1;62(Pt 3):231-4


Influence relevance voting: an accurate and interpretable virtual high throughput screening method

Swamidass SJ, Azencott CA, Lin TW, Gramajo H, Tsai SC, Baldi PJ

Chem Inf Model. 2009, 49, 756


Structure-based inhibitor design of AccD5, an essential acyl-CoA carboxylase carboxyltransferase domain of Mycobacterium tuberculosis

Lin TW, Melgar MM, Kurth D, Swamidass SJ, Purdon J, Tseng T, Gago G, Baldi P, Gramajo H, Tsai SC

Proc Natl Acad Sci U S A. 2006 Feb 28;103(9):3072-7


Structure and Mutagenic Retroevolution of E1 Dehydrase: at the Crossroads of Dehydration, Aminotransfer and Racemization

Smith P, Szu P, Bui C, Liu HW, Tsai SC

Biochemistry, 2008, 47, 6329


Biochemical and structural characterization of an essential acyl coenzyme A carboxylase from Mycobacterium tuberculosis

Gago G, Kurth D, Diacovich L, Tsai SC, Gramajo H

J Bacteriol. 2006 Jan;188(2):477-86


Structural enzymology of aromatic polyketide synthase
Korman TP, Ames BD, Tsai, SC
ACS Volume Based on Polyketides: Biosynthesis, Biological Activity and Genetic Engineering. eds S. R. Baerson; American Chemical Society, 2006


Structural analysis of actinorhodin polyketide ketoreductase: cofactor binding and substrate specificity

Korman TP, Hill JA, Vu TN, Tsai SC

Biochemistry. 2004 Nov 23;43(46):14529-38


Crystal structure of the beta-subunit of acyl-CoA carboxylase: structure-based engineering of substrate specificity

Diacovich L, Mitchell DL, Pham H, Gago G, Melgar MM, Khosla C, Gramajo H, Tsai SC

Biochemistry. 2004 Nov 9;43(44):14027-36


A fine balancing act of type III polyketide synthase

Tsai SC

Chem Biol. 2004 Sep;11(9):1177-8

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