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Publications

25

MIBiG Database

Zdouc, M.M.;* Blin, K.;* Louwen, N.L.L.; Navarro, J.; Loureiro, C.; [142 authors]; Kalkreuter, E.; [136 authors]; van der Hooft, J.J.J.; Linington, R.G.; Weber, T.; Medema, M.H. MIBiG 4.0: advancing biosynthetic gene cluster curation through global collaboration. Nucleic Acids Res. 2024, gkae1115. Link

MiBIG4

24

PKS Domain Structure

Steele, A.D.; Meng, S.; Li, G.; Kalkreuter, E.; Chang, C.; Shen, B. Structural insights into the mechanism of a polyketide synthase thiocysteine lyase domain. J. Am. Chem. Soc. 2024, 146, 32605-32617. Link

SH_Structure
Tetrayne enediyne precursor

23

Unified Enediyne Biosynthesis

Gui, C.;* Kalkreuter, E.;* Lauterbach, L.; Yang, D.; Shen, B. Enediyne biosynthesis unified by an iodinated linear tetrayne intermediate. Nat. Chem. Biol. 2024, 20, 1210-1219. Link

22

Natural Products Discovery Center

Kalkreuter, E.;* Kautsar, S.A.;* Yang, D.;* Teijaro, C.N.;* Bader, C.D.;* Fluegel, L.L.;† Davis, C.M.;† Simpson, J.R.;† Steele, A.D.; Gui, C.; Meng, S.; Li, G.; Viehrig, K.; Ye, F.; Su, P.; Kiefer, A.F.; Lauterbach, L.; Nichols, A.; Cepeda, A.J.; Yan, W.; Fan, B.; Jiang, Y.; Adhikari, A.; Zheng, C.-J.; Shen, B. The Natural Products Discovery Center: release of the first 8490 sequenced strains for exploring Actinobacteria biosynthetic diversity. bioRxiv 2023, 2023.12.14.571759. Link

NPDC
AT-TE

21

PKS ATs and TEs

Steele, A.D.; Jiang, H.; Pan, G.; Lim, S.-K.; Kalkreuter, E.; Kwong, T.; Ju, J.; Rajski, S.; Shen, B. Discrete acyltransferases and thioesterases in iso-migrastatin and lactimidomycin biosynthesis. Biochemistry, 2024, 63, 563-575. Link

20

Microbial Platform Engineering

Fluegel, L.L.;* Deng, M.;* Su, P.;* Kalkreuter, E.; Yang, D.; Rudolf, J.D.; Dong, L.-B.; Shen, B. Development of platensimycin, platencin, and platensilin overproducers by biosynthetic pathway engineering and fermentation medium optimization. J. Ind. Microbiol. Biotechnol., 2024, 51, kuae003. Link

PTM CRISPR
TnmJK2

19

Cofactorless Oxygenases

Gui, C.;* Kalkreuter, E.;* Liu, Y.-C.; Li, G.; Steele, A.D.; Yang, D.; Chang, C.; Shen, B. Cofactorless oxygenases guide anthraquinone-fused enediyne biosynthesis. Nat. Chem. Biol., 2024, 20, 243-250. Link

18

Enediyne Origins

Bhardwaj, M.; Cui, Z.; Hankore, F.D.; Moonschi, F.H.; Esfahani, H.S.; Kalkreuter, E.; Gui, C.; Yang, D.; Phillips Jr., G.N.; Thorson, J.S.; Shen, B.; Van Lanen, S.G. A discrete intermediate for the biosynthesis of both the enediyne core and the anthraquinone moiety of enediyne natural products. Proc. Natl. Acad. Sci. USA, 2023, 120, e2220468120. Link

Heptaene

17

MiBIG3

MIBiG Database

Terlouw, B.R.; Blin, K.; Navarro-Muñoz, J.C.; Avalon, N.E.; Chevrette, M.G.; Egbert, S.; Lee, S.; Meijer, D.; Recchia, M.J.J.; Reitz, Z.L.; van Santen, J.A.; Selem-Mojica, N.; Tørring, T.; Zaroubi, L.; [25 authors]; Kalkreuter, E.; [38 authors]; Collemare, J.; Linington, R.G.; Weber, T.; Medema, M.H. MIBiG 3.0: a community-driven effort to annotate experimentally validated biosynthetic gene clusters. Nucleic Acids Res., 2022, 51, D603-D610. Link

16

Enediyne-Anthraquinone Fusion

Gui, C.*; Kalkreuter, E.*; Liu, Y.-C.; Adhikari, A.; Teijaro, C.N.; Yang, D.; Chang, C.; Shen, B. Intramolecular C-C bond formation links anthraquinone and enediyne scaffolds in tiancimycin biosynthesis. J. Am. Chem. Soc., 2022, 144, 20452-20462. Link

TnmK1

15

MIO-Aminomutases

Enzyme Mechanisms

Kalkreuter, E.; Shen, B. MIO-containing aminomutases for α- to β-amino acids. Trends Chem., 2022, 4, 91-92. Mechanism of the Month. Link

14

PKS SH Domain

Meng, S.; Steele, A.D.; Yan, W.; Pan, G.; Kalkreuter, E.; Liu, Y.-C.; Xu, Z.; Shen, B. Thiocysteine lyases as polyketide synthase domains installing hydropersulfide into natural products and a hydropersulfide methyltransferase. Nat. Commun., 2021, 12, 1-11. Link

GnmSH
DEBS MD

13

MD-Guided PKS Engineering

Kalkreuter, E.; Bingham, K.S.; Keeler, A.M.; Lowell, A.N.; Schmidt, J.J.; Sherman, D.H.; Williams, G.J. Computationally-guided exchange of substrate selectivity motifs in a modular polyketide synthase acyltransferase. Nat. Commun., 2021, 12, 2193. Link

12

Discovery of Thioangucyclines

Cao, M.; Zheng, C.-J.; Yang, D.; Kalkreuter, E.; Adhikari, A.; Liu, Y.-C.; Rateb, M.E.; Shen, B. Cryptic sulfur incorporation in thioangucycline biosynthesis. Angew. Chem. Int. Ed., 2021, 133, 7216-7223. Link

Thioangucyclines
PtmC

11

Thioacid Arylamine N-acyltransferase

Zheng, C.-J.*; Kalkreuter, E.*; Fan, B.-Y.; Liu, Y.-C.; Dong, L.-B.; Shen, B. PtmC catalyzes the final step of thioplatensimycin, thioplatencin, and thioplatensilin biosynthesis and expands the scope of arylamine N-acetyltransferases. ACS Chem. Biol., 2020, 16, 96-105. Link

10

Genome-Guided Natural Product Discovery

Kalkreuter, E.; Pan, G.; Cepeda, A.J.; Shen, B. Targeting bacterial genomes for natural product discovery. Trends Pharmacol. Sci., 2020, 41, 13-26. Feature Review. Link

Genome mining
Hybrid NRPS-PKS

09

Hybrid NRPS-PKSs

Steele, A.D.; Kalkreuter, E.; Pan, G.; Meng, S.; Shen, B. Hybrid peptide-polyketide natural product biosynthesis. In Comprehensive Natural Products III (Third Edition); Liu, H.-W.; Begley, T.P., Eds.; Elsevier: Oxford, 2020; Volume 2, Chapter 13, p 284-335. Link

08

Diterpenoid Monooxygenase

Dong, L.-B.; Liu, Y.-C.; Cepeda, A.J.; Kalkreuter, E.; Deng, M.-R.; Rudolf, J.D.; Chang, C.; Joachimiak, A.J.; Phillips Jr, G.N.; Shen, B. Characterization and crystal structure of a nonheme diiron monooxygenase involved in platensimycin and platencin biosynthesis. J. Am. Chem. Soc., 2019, 141, 12406-12412. Link

PtmU3
FapR

07

Malonyl-CoA Biosensors

Kalkreuter, E.; Keeler, A.M.; Malico, A.A.; Bingham, K.S.; Gayen, A.K.; Williams, G.J. Development of a genetically encoded biosensor for detection of polyketide synthase extender units in Escherichia coli. ACS Synth. Biol., 2019, 8, 1391-1400. Link

06

Three-Enzyme Diterpenoid Oxidation

Dong, L.-B.; Zhang, X.; Rudolf, J.D.; Deng, M.-R.; Kalkreuter, E.; Cepeda, A.J.; Renata, H.; Shen, B. Cryptic and stereospecific hydroxylation, oxidation, and reduction in platensimycin and platencin biosynthesis. J. Am. Chem. Soc., 2019, 141, 4043-4050. Link

PtmO3O8O1_WebTOC_edited.png
Pik PKS Engineering

05

Bimodular PKS Engineering

Kalkreuter, E.; CroweTipton, J.M.; Lowell, A.N.; Sherman, D.H.; Williams, G.J. Engineering the substrate specificity of a modular polyketide synthase for installation of consecutive non-natural extender units. J. Am. Chem. Soc., 2019, 141, 1961-1969. Link

04

Precursor-Directed Biosynthesis

Kalkreuter, E.; Carpenter, S.M.; Williams, G.J. Precursor-directed biosynthesis and semi-synthesis. In Chemical and Biological Synthesis; Westwood, N.J.; Nelson, A., Eds.; The Royal Society of Chemistry: London, 2018; Chapter 11, p 275-312. Link

Precursor-directed biosynthesis
Engineering PKSs & NRPSs

03

NRPS and PKS Engineering

Kalkreuter, E.; Williams, G.J. Engineering enzymatic assembly lines for the production of new antimicrobials. Curr. Op. Microbiol., 2018, 45, 140-148. Link

02

Nitric Oxide in Prostate Cancer

Sun, Q.; Kalkreuter, E.; Sun, C.Q.; Arnold, R.S.; Petros, J.A. Mitochondrial DNA mutations enhance proliferation via modulation of cellular nitric oxide, an effect amenable to pharmacologic manipulation. J. Urol., 2013, 189, e88-e89. Link

01

Stem Cell Patents

Shyntum, Y.; Kalkreuter, E. Stem cell patents—reexamination/litigation—the last 5 years. Tissue. Eng. Part B Rev., 2009, 15, 87-90. Link

Kalkreuter Lab

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