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Methylations in complex carbapenem biosynthesis are catalyzed by a single cobalamin-dependent radical S-adenosylmethionine enzyme.

Sinner EK, Lichstrahl MS, Li R, Marous DR, Townsend CA.

Chem Commun (Camb). 2019 Dec 10;55(99):14934-14937. doi: 10.1039/c9cc07197k.


Structure of a bound peptide phosphonate reveals the mechanism of nocardicin bifunctional thioesterase epimerase-hydrolase half-reactions.

Patel KD, d'Andrea FB, Gaudelli NM, Buller AR, Townsend CA, Gulick AM.

Nat Commun. 2019 Aug 27;10(1):3868. doi: 10.1038/s41467-019-11740-6.


Late-Stage Conversion of Diphenylphosphonate to Fluorophosphonate Probes for the Investigation of Serine Hydrolases.

d'Andrea FB, Townsend CA.

Cell Chem Biol. 2019 Jun 20;26(6):878-884.e8. doi: 10.1016/j.chembiol.2019.02.020. Epub 2019 Apr 11.


Exploring Fungal Polyketide C-Methylation through Combinatorial Domain Swaps.

Storm PA, Pal P, Huitt-Roehl CR, Townsend CA.

ACS Chem Biol. 2018 Nov 16;13(11):3043-3048. doi: 10.1021/acschembio.8b00429. Epub 2018 Oct 30.


The architectures of iterative type I PKS and FAS.

Herbst DA, Townsend CA, Maier T.

Nat Prod Rep. 2018 Oct 17;35(10):1046-1069. doi: 10.1039/c8np00039e. Review.


Gene cluster conservation provides insight into cercosporin biosynthesis and extends production to the genus Colletotrichum.

de Jonge R, Ebert MK, Huitt-Roehl CR, Pal P, Suttle JC, Spanner RE, Neubauer JD, Jurick WM 2nd, Stott KA, Secor GA, Thomma BPHJ, Van de Peer Y, Townsend CA, Bolton MD.

Proc Natl Acad Sci U S A. 2018 Jun 12;115(24):E5459-E5466. doi: 10.1073/pnas.1712798115. Epub 2018 May 29. Erratum in: Proc Natl Acad Sci U S A. 2018 Aug 28;115(35):E8324.


Mechanism of Integrated β-Lactam Formation by a Nonribosomal Peptide Synthetase during Antibiotic Synthesis.

Long DH, Townsend CA.

Biochemistry. 2018 Jun 19;57(24):3353-3358. doi: 10.1021/acs.biochem.8b00411. Epub 2018 May 3.


Chromobacterium spp. mediate their anti-Plasmodium activity through secretion of the histone deacetylase inhibitor romidepsin.

Saraiva RG, Huitt-Roehl CR, Tripathi A, Cheng YQ, Bosch J, Townsend CA, Dimopoulos G.

Sci Rep. 2018 Apr 18;8(1):6176. doi: 10.1038/s41598-018-24296-0.


The structural organization of substrate loading in iterative polyketide synthases.

Herbst DA, Huitt-Roehl CR, Jakob RP, Kravetz JM, Storm PA, Alley JR, Townsend CA, Maier T.

Nat Chem Biol. 2018 May;14(5):474-479. doi: 10.1038/s41589-018-0026-3. Epub 2018 Apr 2.


Characterization of an Anthracene Intermediate in Dynemicin Biosynthesis.

Cohen DR, Townsend CA.

Angew Chem Int Ed Engl. 2018 May 14;57(20):5650-5654. doi: 10.1002/anie.201802036. Epub 2018 Mar 24.


A dual role for a polyketide synthase in dynemicin enediyne and anthraquinone biosynthesis.

Cohen DR, Townsend CA.

Nat Chem. 2018 Feb;10(2):231-236. doi: 10.1038/nchem.2876. Epub 2017 Nov 20.


In trans hydrolysis of carrier protein-bound acyl intermediates by CitA during citrinin biosynthesis.

Storm PA, Townsend CA.

Chem Commun (Camb). 2017 Dec 19;54(1):50-53. doi: 10.1039/c7cc07079a.


Monobactam formation in sulfazecin by a nonribosomal peptide synthetase thioesterase.

Oliver RA, Li R, Townsend CA.

Nat Chem Biol. 2018 Jan;14(1):5-7. doi: 10.1038/nchembio.2526. Epub 2017 Nov 20.


Whole-Genome Shotgun Sequencing of Two β-Proteobacterial Species in Search of the Bulgecin Biosynthetic Cluster.

Horsman ME, Marous DR, Li R, Oliver RA, Byun B, Emrich SJ, Boggess B, Townsend CA, Mobashery S.

ACS Chem Biol. 2017 Oct 20;12(10):2552-2557. doi: 10.1021/acschembio.7b00687. Epub 2017 Sep 26.


Unusual Blue-Shifted Acid-Responsive Photoluminescence Behavior in 6-Amino-8-cyanobenzo[1,2-b]indolizines.

Outlaw VK, Zhou J, Bragg AE, Townsend CA.

RSC Adv. 2016 Jul 8;6(66):61249-61253. doi: 10.1039/C6RA10605F. Epub 2016 Jun 3.


LdtMav2, a nonclassical transpeptidase and susceptibility of Mycobacterium avium to carbapenems.

Mattoo R, Lloyd EP, Kaushik A, Kumar P, Brunelle JL, Townsend CA, Lamichhane G.

Future Microbiol. 2017 Jun;12:595-607. doi: 10.2217/fmb-2016-0208. Epub 2017 May 30.


Structural insight into the inactivation of Mycobacterium tuberculosis non-classical transpeptidase LdtMt2 by biapenem and tebipenem.

Bianchet MA, Pan YH, Basta LAB, Saavedra H, Lloyd EP, Kumar P, Mattoo R, Townsend CA, Lamichhane G.

BMC Biochem. 2017 May 25;18(1):8. doi: 10.1186/s12858-017-0082-4.


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. doi: 10.1073/pnas.1609001114. Epub 2017 May 8.


Functional and Structural Analysis of Programmed C-Methylation in the Biosynthesis of the Fungal Polyketide Citrinin.

Storm PA, Herbst DA, Maier T, Townsend CA.

Cell Chem Biol. 2017 Mar 16;24(3):316-325. doi: 10.1016/j.chembiol.2017.01.008. Epub 2017 Feb 23.


Identification and Characterization of the Sulfazecin Monobactam Biosynthetic Gene Cluster.

Li R, Oliver RA, Townsend CA.

Cell Chem Biol. 2017 Jan 19;24(1):24-34. doi: 10.1016/j.chembiol.2016.11.010. Epub 2016 Dec 22.


Non-classical transpeptidases yield insight into new antibacterials.

Kumar P, Kaushik A, Lloyd EP, Li SG, Mattoo R, Ammerman NC, Bell DT, Perryman AL, Zandi TA, Ekins S, Ginell SL, Townsend CA, Freundlich JS, Lamichhane G.

Nat Chem Biol. 2017 Jan;13(1):54-61. doi: 10.1038/nchembio.2237. Epub 2016 Nov 7.


Convergent biosynthetic pathways to β-lactam antibiotics.

Townsend CA.

Curr Opin Chem Biol. 2016 Dec;35:97-108. doi: 10.1016/j.cbpa.2016.09.013. Epub 2016 Sep 29. Review.


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. doi: 10.1002/anie.201605401.


Quenching of pH-Responsive Luminescence of a Benzoindolizine Sensor by an Ultrafast Hydrogen Shift.

Zhou J, Outlaw VK, Townsend CA, Bragg AE.

Chemistry. 2016 Oct 17;22(43):15212-15215. doi: 10.1002/chem.201603284. Epub 2016 Sep 13.


Molecular Characterization of the Cercosporin Biosynthetic Pathway in the Fungal Plant Pathogen Cercospora nicotianae.

Newman AG, Townsend CA.

J Am Chem Soc. 2016 Mar 30;138(12):4219-28. doi: 10.1021/jacs.6b00633. Epub 2016 Mar 16.


Loss of a Functionally and Structurally Distinct ld-Transpeptidase, LdtMt5, Compromises Cell Wall Integrity in Mycobacterium tuberculosis.

Brammer Basta LA, Ghosh A, Pan Y, Jakoncic J, Lloyd EP, Townsend CA, Lamichhane G, Bianchet MA.

J Biol Chem. 2015 Oct 16;290(42):25670-85. doi: 10.1074/jbc.M115.660753. Epub 2015 Aug 24.


New Insights into the Conversion of Versicolorin A in the Biosynthesis of Aflatoxin B1.

Conradt D, Schätzle MA, Haas J, Townsend CA, Müller M.

J Am Chem Soc. 2015 Sep 2;137(34):10867-9. doi: 10.1021/jacs.5b06770. Epub 2015 Aug 19.


Consecutive radical S-adenosylmethionine methylations form the ethyl side chain in thienamycin biosynthesis.

Marous DR, Lloyd EP, Buller AR, Moshos KA, Grove TL, Blaszczyk AJ, Booker SJ, Townsend CA.

Proc Natl Acad Sci U S A. 2015 Aug 18;112(33):10354-8. doi: 10.1073/pnas.1508615112. Epub 2015 Aug 3.


One-pot synthesis of highly substituted N-fused heteroaromatic bicycles from azole aldehydes.

Outlaw VK, d'Andrea FB, Townsend CA.

Org Lett. 2015 Apr 17;17(8):1822-5. doi: 10.1021/ol5036936. Epub 2015 Mar 27.


Starter unit flexibility for engineered product synthesis by the nonreducing polyketide synthase PksA.

Huitt-Roehl CR, Hill EA, Adams MM, Vagstad AL, Li JW, Townsend CA.

ACS Chem Biol. 2015 Jun 19;10(6):1443-9. doi: 10.1021/acschembio.5b00005. Epub 2015 Mar 10.


β-Lactam formation by a non-ribosomal peptide synthetase during antibiotic biosynthesis.

Gaudelli NM, Long DH, Townsend CA.

Nature. 2015 Apr 16;520(7547):383-7. doi: 10.1038/nature14100. Epub 2015 Jan 26.


A practical route to substituted 7-aminoindoles from pyrrole-3-carboxaldehydes.

Outlaw VK, Townsend CA.

Org Lett. 2014 Dec 19;16(24):6334-7. doi: 10.1021/ol503078h. Epub 2014 Dec 5.


Aflatoxin and deconstruction of type I, iterative polyketide synthase function.

Townsend CA.

Nat Prod Rep. 2014 Oct;31(10):1260-5. doi: 10.1039/c4np00092g. Review.


Exploring the role of conformational heterogeneity in cis-autoproteolytic activation of ThnT.

Buller AR, Freeman MF, Schildbach JF, Townsend CA.

Biochemistry. 2014 Jul 8;53(26):4273-81. doi: 10.1021/bi500385d. Epub 2014 Jun 26.


Systematic domain swaps of iterative, nonreducing polyketide synthases provide a mechanistic understanding and rationale for catalytic reprogramming.

Newman AG, Vagstad AL, Storm PA, Townsend CA.

J Am Chem Soc. 2014 May 21;136(20):7348-62. doi: 10.1021/ja5007299. Epub 2014 May 9.


Epimerization and substrate gating by a TE domain in β-lactam antibiotic biosynthesis.

Gaudelli NM, Townsend CA.

Nat Chem Biol. 2014 Apr;10(4):251-8. doi: 10.1038/nchembio.1456. Epub 2014 Feb 16.


Identification and characterization of the carbapenem MM 4550 and its gene cluster in Streptomyces argenteolus ATCC 11009.

Li R, Lloyd EP, Moshos KA, Townsend CA.

Chembiochem. 2014 Jan 24;15(2):320-31. doi: 10.1002/cbic.201300319. Epub 2014 Jan 13.


Enzymology: Modular biosynthesis branches out.

Townsend CA.

Nature. 2013 Oct 3;502(7469):44-5. doi: 10.1038/nature12562. Epub 2013 Sep 18. No abstract available.


Biochemical determination of enzyme-bound metabolites: preferential accumulation of a programmed octaketide on the enediyne polyketide synthase CalE8.

Belecki K, Townsend CA.

J Am Chem Soc. 2013 Sep 25;135(38):14339-48. doi: 10.1021/ja406697t. Epub 2013 Sep 17.


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. doi: 10.1016/j.chembiol.2013.07.012. Epub 2013 Aug 29. Erratum in: Chem Biol. 2014 Jul 17;21(7):913. Haushalter, Bob [corrected to Haushalter, Robert W]; Vagstad, Anna [corrected to Vagstad, Anna L].


Stereocontrolled syntheses of peptide thioesters containing modified seryl residues as probes of antibiotic biosynthesis.

Gaudelli NM, Townsend CA.

J Org Chem. 2013 Jul 5;78(13):6412-26. doi: 10.1021/jo4007893. Epub 2013 Jun 18. Erratum in: J Org Chem. 2013 Nov 1;78(21):11115.


Mechanistic insights into the bifunctional non-heme iron oxygenase carbapenem synthase by active site saturation mutagenesis.

Phelan RM, Townsend CA.

J Am Chem Soc. 2013 May 22;135(20):7496-502. doi: 10.1021/ja311078s. Epub 2013 May 13.


Intrinsic evolutionary constraints on protease structure, enzyme acylation, and the identity of the catalytic triad.

Buller AR, Townsend CA.

Proc Natl Acad Sci U S A. 2013 Feb 19;110(8):E653-61. doi: 10.1073/pnas.1221050110. Epub 2013 Feb 4.


Non-ribosomal propeptide precursor in nocardicin A biosynthesis predicted from adenylation domain specificity dependent on the MbtH family protein NocI.

Davidsen JM, Bartley DM, Townsend CA.

J Am Chem Soc. 2013 Feb 6;135(5):1749-59. doi: 10.1021/ja307710d. Epub 2013 Jan 18.


Combinatorial domain swaps provide insights into the rules of fungal polyketide synthase programming and the rational synthesis of non-native aromatic products.

Vagstad AL, Newman AG, Storm PA, Belecki K, Crawford JM, Townsend CA.

Angew Chem Int Ed Engl. 2013 Feb 4;52(6):1718-21. doi: 10.1002/anie.201208550. Epub 2013 Jan 2. No abstract available.


Characterization of a fungal thioesterase having Claisen cyclase and deacetylase activities in melanin biosynthesis.

Vagstad AL, Hill EA, Labonte JW, Townsend CA.

Chem Biol. 2012 Dec 21;19(12):1525-34. doi: 10.1016/j.chembiol.2012.10.002.


Active site comparisons and catalytic mechanisms of the hot dog superfamily.

Labonte JW, Townsend CA.

Chem Rev. 2013 Mar 13;113(3):2182-204. doi: 10.1021/cr300169a. Epub 2012 Dec 3. Review. No abstract available.


Analysis of the cercosporin polyketide synthase CTB1 reveals a new fungal thioesterase function.

Newman AG, Vagstad AL, Belecki K, Scheerer JR, Townsend CA.

Chem Commun (Camb). 2012 Dec 14;48(96):11772-4. doi: 10.1039/c2cc36010a. Epub 2012 Oct 29.


Environmental control of the calicheamicin polyketide synthase leads to detection of a programmed octaketide and a proposal for enediyne biosynthesis.

Belecki K, Townsend CA.

Angew Chem Int Ed Engl. 2012 Nov 5;51(45):11316-9. doi: 10.1002/anie.201206462. Epub 2012 Oct 8.

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