Data Science-Driven Analysis of Substrate-Permissive Diketopiperazine Reverse Prenyltransferase NotF: Applications in Protein Engineering and Cascade Biocatalytic Synthesis of (-)-Eurotiumin A

Kelly, Samantha P.; Shende, Vikram V.; Flynn, Autumn R.; Dan, Qingyun; Ye, Ying; Smith, Janet L.; Tsukamoto, Sachiko; Sigman, Matthew S.; Sherman, David H.

doi:10.1021/jacs.2c06631

Data Science-Driven Analysis of Substrate-Permissive Diketopiperazine Reverse Prenyltransferase NotF: Applications in Protein Engineering and Cascade Biocatalytic Synthesis of (-)-Eurotiumin A

Journal Article · Wed Oct 12 00:00:00 EDT 2022 · Journal of the American Chemical Society

DOI:https://doi.org/10.1021/jacs.2c06631· OSTI ID:1994337

^[1]; ^[2]; ^[3]; ^[4]; Ye, Ying ^[5]; ^[1]; ^[6]; ^[3]; ^[7]

University of Michigan, Ann Arbor, MI (United States)
University of Michigan, Ann Arbor, MI (United States); University of California, San Diego, CA (United States). Scripps Inst. of Oceanography
University of Utah, Salt Lake City, UT (United States)
University of Michigan, Ann Arbor, MI (United States); Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States). Joint BioEnergy Institute
University of Michigan, Ann Arbor, MI (United States); University of Science and Technology Wuhan (China)
Kumamoto University (Japan)
davidhs@umich.edu

Prenyltransfer is an early-stage carbon-hydrogen bond (C-H) functionalization prevalent in the biosynthesis of a diverse array of biologically active bacterial, fungal, plant, and metazoan diketopiperazine (DKP) alkaloids. Toward the development of a unified strategy for biocatalytic construction of prenylated DKP indole alkaloids, we sought to identify and characterize a substrate-permissive C2 reverse prenyltransferase (PT). As the first tailoring event within the biosynthesis of cytotoxic notoamide metabolites, PT NotF catalyzes C2 reverse prenyltransfer of brevianamide F. Solving a crystal structure of NotF (in complex with native substrate and prenyl donor mimic dimethylallyl S-thiolodiphosphate (DMSPP)) revealed a large, solvent-exposed active site, intimating NotF may possess a significantly broad substrate scope. To assess the substrate selectivity of NotF, we synthesized a panel of 30 sterically and electronically differentiated tryptophanyl DKPs, the majority of which were selectively prenylated by NotF in synthetically useful conversions (2 to > 99%). Quantitative representation of this substrate library and development of a descriptive statistical model provided insight into the molecular origins of NotF's substrate promiscuity. This approach enabled the identification of key substrate descriptors (electrophilicity, size, and flexibility) that govern the rate of NotF-catalyzed prenyltransfer, and the development of an "induced fit docking (IFD)-guided" engineering strategy for improved turnover of our largest substrates. We further demonstrated the utility of NotF in tandem with oxidative cyclization using flavin monooxygenase, BvnB. This one-pot, in vitro biocatalytic cascade enabled the first chemoenzymatic synthesis of the marine fungal natural product, (-)-eurotiumin A, in three steps and 60% overall yield.

View Accepted Manuscript (DOE)

Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER); National Science Foundation (NSF); National Institutes of Health (NIH); Hans W. Vahlteich Professorship; Margaret J. Hunter Professorship; National Cancer Institute; National Institute of General Medical Sciences

Grant/Contract Number:: AC02-05CH11231; AC02-06CH11357

OSTI ID:: 1994337

Alternate ID(s):: OSTI ID: 1901248

Journal Information:: Journal of the American Chemical Society, Journal Name: Journal of the American Chemical Society Journal Issue: 42 Vol. 144; ISSN 0002-7863

Publisher:: American Chemical Society (ACS)Copyright Statement

Country of Publication:: United States

Language:: English

References (73)

A Stepwise Huisgen Cycloaddition Process: Copper(I)-Catalyzed Regioselective “Ligation” of Azides and Terminal Alkynes Rostovtsev, Vsevolod V.; Green, Luke G.; Fokin, Valery V. Angewandte Chemie International Edition, Vol. 41, Issue 14, p. 2596-2599 https://doi.org/10.1002/1521-3773(20020715)41:14<2596::AID-ANIE2596>3.0.CO;2-4	journal	July 2002
Notoamides A–D: Prenylated Indole Alkaloids Isolated from a Marine-Derived Fungus,Aspergillus sp. Kato, Hikaru; Yoshida, Takushi; Tokue, Takanori Angewandte Chemie International Edition, Vol. 46, Issue 13 https://doi.org/10.1002/anie.200604381	journal	March 2007
Biosynthesis of Complex Indole Alkaloids: Elucidation of the Concise Pathway of Okaramines Lai, Chen-Yu; Lo, I-Wen; Hewage, Ranuka T. Angewandte Chemie International Edition, Vol. 56, Issue 32 https://doi.org/10.1002/anie.201705501	journal	July 2017
Three Novel, Structurally Unique Spirocyclic Alkaloids from the Halotolerant B-17 Fungal Strain ofAspergillus variecolor Wang, Wen-Liang; Zhu, Tian-Jiao; Tao, Hong-Wen Chemistry & Biodiversity, Vol. 4, Issue 12 https://doi.org/10.1002/cbdv.200790240	journal	December 2007
Flavin‐Dependent Monooxygenases NotI and NotI′ Mediate Spiro‐Oxindole Formation in Biosynthesis of the Notoamides Fraley, Amy E.; Tran, Hong T.; Kelly, Samantha P. ChemBioChem, Vol. 21, Issue 17 https://doi.org/10.1002/cbic.202000004	journal	May 2020
Predicting the Substrate Scope of the Flavin‐Dependent Halogenase BrvH Neubauer, Pia R.; Pienkny, Silke; Wessjohann, Ludger ChemBioChem, Vol. 21, Issue 22 https://doi.org/10.1002/cbic.202000444	journal	August 2020
Structure, Bioactivity and Synthesis of Natural Products with Hexahydropyrrolo[2,3-b]indole Ruiz-Sanchis, Pau; Savina, Svetlana A.; Albericio, Fernando Chemistry - A European Journal, Vol. 17, Issue 5 https://doi.org/10.1002/chem.201001451	journal	January 2011
Bioorthogonal Click Chemistry: Covalent Labeling in Living Systems Baskin, Jeremy M.; Bertozzi, Carolyn R. QSAR & Combinatorial Science, Vol. 26, Issue 11-12 https://doi.org/10.1002/qsar.200740086	journal	December 2007
The ABBA family of aromatic prenyltransferases: broadening natural product diversity Tello, M.; Kuzuyama, T.; Heide, L. Cellular and Molecular Life Sciences, Vol. 65, Issue 10 https://doi.org/10.1007/s00018-008-7579-3	journal	February 2008
Reinvestigation of the substrate specificity of a reverse prenyltransferase NotF from Aspergillus sp. MF297-2 Yang, Keyan; Li, Shu-Ming; Liu, Xiaoqing Archives of Microbiology, Vol. 202, Issue 6 https://doi.org/10.1007/s00203-020-01854-7	journal	March 2020
Applications of dimethylallyltryptophan synthases and other indole prenyltransferases for structural modification of natural products Li, Shu-Ming Applied Microbiology and Biotechnology, Vol. 84, Issue 4 https://doi.org/10.1007/s00253-009-2128-z	journal	July 2009
Identification of a brevianamide F reverse prenyltransferase BrePT from Aspergillus versicolor with a broad substrate specificity towards tryptophan-containing cyclic dipeptides Yin, Suqin; Yu, Xia; Wang, Qing Applied Microbiology and Biotechnology, Vol. 97, Issue 4 https://doi.org/10.1007/s00253-012-4130-0	journal	June 2012
Prenyltransferases as key enzymes in primary and secondary metabolism Winkelblech, Julia; Fan, Aili; Li, Shu-Ming Applied Microbiology and Biotechnology, Vol. 99, Issue 18 https://doi.org/10.1007/s00253-015-6811-y	journal	July 2015
Enzymatic studies on aromatic prenyltransferases Mori, Takahiro Journal of Natural Medicines, Vol. 74, Issue 3 https://doi.org/10.1007/s11418-020-01393-x	journal	March 2020
Purification and properties of dimethylallylpyrophosphate: Tryptophan dimethylallyl transferase, the first enzyme of ergot alkaloid biosynthesis in Claviceps. sp. SD 58 Lee, Siu-Leung; Floss, Heinz G.; Heinstein, Peter Archives of Biochemistry and Biophysics, Vol. 177, Issue 1 https://doi.org/10.1016/0003-9861(76)90418-5	journal	November 1976
Austamide, a new toxic metabolite from Steyn, P. S. Tetrahedron Letters, Vol. 12, Issue 36 https://doi.org/10.1016/S0040-4039(01)97170-9	journal	January 1971
Bio-mining the microbial treasures of the ocean: New natural products Imhoff, Johannes F.; Labes, Antje; Wiese, Jutta Biotechnology Advances, Vol. 29, Issue 5 https://doi.org/10.1016/j.biotechadv.2011.03.001	journal	September 2011
Catalytic Mechanism of Stereospecific Formation of cis-Configured Prenylated Pyrroloindoline Diketopiperazines by Indole Prenyltransferases Yu, Xia; Zocher, Georg; Xie, Xiulan Chemistry & Biology, Vol. 20, Issue 12 https://doi.org/10.1016/j.chembiol.2013.10.007	journal	December 2013
Structure and Catalytic Mechanism of a Cyclic Dipeptide Prenyltransferase with Broad Substrate Promiscuity Schuller, Jan Michael; Zocher, Georg; Liebhold, Mike Journal of Molecular Biology, Vol. 422, Issue 1 https://doi.org/10.1016/j.jmb.2012.05.033	journal	September 2012
Evolution of aromatic prenyltransferases in the biosynthesis of indole derivatives Li, Shu-Ming Phytochemistry, Vol. 70, Issue 15-16 https://doi.org/10.1016/j.phytochem.2009.03.019	journal	October 2009
Concise, biomimetic total synthesis of d,l-marcfortine C Greshock, Thomas J.; Grubbs, Alan W.; Williams, Robert M. Tetrahedron, Vol. 63, Issue 27 https://doi.org/10.1016/j.tet.2007.03.016	journal	July 2007
Concise syntheses of the 1,7-dihydropyrano[2,3-g]indole ring system of the stephacidins, aspergamides and norgeamides Grubbs, Alan W.; Artman, Gerald D.; Williams, Robert M. Tetrahedron Letters, Vol. 46, Issue 52 https://doi.org/10.1016/j.tetlet.2005.10.112	journal	December 2005
Pursuit of Noncovalent Interactions for Strategic Site-Selective Catalysis Toste, F. Dean; Sigman, Matthew S.; Miller, Scott J. Accounts of Chemical Research, Vol. 50, Issue 3 https://doi.org/10.1021/acs.accounts.6b00613	journal	March 2017
(±)-Uncarilins A and B, Dimeric Isoechinulin-Type Alkaloids from Uncaria rhynchophylla Geng, Chang-An; Huang, Xiao-Yan; Ma, Yun-Bao Journal of Natural Products, Vol. 80, Issue 4 https://doi.org/10.1021/acs.jnatprod.6b00938	journal	February 2017
Bioinspired Indole Prenylation Reactions in Water Tanaka, Satomi; Shiomi, Shinya; Ishikawa, Hayato Journal of Natural Products, Vol. 80, Issue 8 https://doi.org/10.1021/acs.jnatprod.7b00464	journal	August 2017
Lewis Acid Catalyzed Displacement of Trichloroacetimidates in the Synthesis of Functionalized Pyrroloindolines Adhikari, Arijit A.; Chisholm, John D. Organic Letters, Vol. 18, Issue 16 https://doi.org/10.1021/acs.orglett.6b02024	journal	August 2016
A Mild and General Larock Indolization Protocol for the Preparation of Unnatural Tryptophans Chuang, Kangway V.; Kieffer, Madeleine E.; Reisman, Sarah E. Organic Letters, Vol. 18, Issue 18 https://doi.org/10.1021/acs.orglett.6b02477	journal	September 2016
Molecular Basis of Iterative C–H Oxidation by TamI, a Multifunctional P450 Monooxygenase from the Tirandamycin Biosynthetic Pathway Newmister, Sean A.; Srivastava, Kinshuk Raj; Espinoza, Rosa V. ACS Catalysis, Vol. 10, Issue 22 https://doi.org/10.1021/acscatal.0c03248	journal	November 2020
Machine Learning in Enzyme Engineering Mazurenko, Stanislav; Prokop, Zbynek; Damborsky, Jiri ACS Catalysis, Vol. 10, Issue 2 https://doi.org/10.1021/acscatal.9b04321	journal	December 2019
Inversion of Extender Unit Selectivity in the Erythromycin Polyketide Synthase by Acyltransferase Domain Engineering Koryakina, Irina; Kasey, Christian; McArthur, John B. ACS Chemical Biology, Vol. 12, Issue 1 https://doi.org/10.1021/acschembio.6b00732	journal	November 2016
Biosynthesis and Structure–Activity Relationship Studies of Okaramines That Target Insect Glutamate-Gated Chloride Channels Kato, Naoki; Furutani, Shogo; Otaka, Junnosuke ACS Chemical Biology, Vol. 13, Issue 3 https://doi.org/10.1021/acschembio.7b00878	journal	January 2018
An Artificial Pathway for Isoprenoid Biosynthesis Decoupled from Native Hemiterpene Metabolism Lund, Sean; Hall, Rachael; Williams, Gavin J. ACS Synthetic Biology, Vol. 8, Issue 2 https://doi.org/10.1021/acssynbio.8b00383	journal	January 2019
Quantitative Analysis of Substrate Specificity of Haloalkane Dehalogenase LinB from Sphingomonas paucimobilis UT26 Kmunícek, Jan; Hynková, Kamila; Jedlicka, Tomás Biochemistry, Vol. 44, Issue 9 https://doi.org/10.1021/bi047912o	journal	February 2005
Tyrosine O -Prenyltransferase SirD Catalyzes S -, C -, and N -Prenylations on Tyrosine and Tryptophan Derivatives Rudolf, Jeffrey D.; Poulter, C. Dale ACS Chemical Biology, Vol. 8, Issue 12 https://doi.org/10.1021/cb400691z	journal	October 2013
Monoisoprenylated cyclo-L-alanyl-L-tryptophanyl. Biosynthetic precursor of echinulin Allen, Charles M. Journal of the American Chemical Society, Vol. 95, Issue 7 https://doi.org/10.1021/ja00788a059	journal	April 1973
Genome-Based Characterization of Two Prenylation Steps in the Assembly of the Stephacidin and Notoamide Anticancer Agents in a Marine-Derived Aspergillus sp. Ding, Yousong; Wet, Jeffrey R. de; Cavalcoli, James Journal of the American Chemical Society, Vol. 132, Issue 36 https://doi.org/10.1021/ja1049302	journal	September 2010
Structure−Function Analysis of an Enzymatic Prenyl Transfer Reaction Identifies a Reaction Chamber with Modifiable Specificity Jost, Marco; Zocher, Georg; Tarcz, Sylwia Journal of the American Chemical Society, Vol. 132, Issue 50 https://doi.org/10.1021/ja106817c	journal	November 2010
Multisite Prenylation of 4-Substituted Tryptophans by Dimethylallyltryptophan Synthase Rudolf, Jeffrey D.; Wang, Hong; Poulter, C. Dale Journal of the American Chemical Society, Vol. 135, Issue 5 https://doi.org/10.1021/ja310734n	journal	January 2013
Mechanism of Dimethylallyltryptophan Synthase: Evidence for a Dimethylallyl Cation Intermediate in an Aromatic Prenyltransferase Reaction Luk, Louis Y. P.; Tanner, Martin E. Journal of the American Chemical Society, Vol. 131, Issue 39 https://doi.org/10.1021/ja906485u	journal	September 2009
Total Synthesis of Gypsetin, Deoxybrevianamide E, Brevianamide E, and Tryprostatin B: Novel Constructions of 2,3-Disubstituted Indoles Schkeryantz, Jeffrey M.; Woo, Jonathan C. G.; Siliphaivanh, Phieng Journal of the American Chemical Society, Vol. 121, Issue 51 https://doi.org/10.1021/ja9925249	journal	December 1999
Discovery and Biocatalytic Application of a PLP-Dependent Amino Acid γ-Substitution Enzyme That Catalyzes C–C Bond Formation Chen, Mengbin; Liu, Chun-Ting; Tang, Yi Journal of the American Chemical Society, Vol. 142, Issue 23 https://doi.org/10.1021/jacs.0c03535	journal	May 2020
Computational-Based Mechanistic Study and Engineering of Cytochrome P450 MycG for Selective Oxidation of 16-Membered Macrolide Antibiotics Yang, Song; DeMars, Matthew D.; Grandner, Jessica M. Journal of the American Chemical Society, Vol. 142, Issue 42 https://doi.org/10.1021/jacs.0c04388	journal	October 2020
Structure and Function of NzeB, a Versatile C–C and C–N Bond-Forming Diketopiperazine Dimerase Shende, Vikram V.; Khatri, Yogan; Newmister, Sean A. Journal of the American Chemical Society, Vol. 142, Issue 41 https://doi.org/10.1021/jacs.0c06312	journal	August 2020
Function and Structure of MalA/MalA′, Iterative Halogenases for Late-Stage C–H Functionalization of Indole Alkaloids Fraley, Amy E.; Garcia-Borràs, Marc; Tripathi, Ashootosh Journal of the American Chemical Society, Vol. 139, Issue 34 https://doi.org/10.1021/jacs.7b06773	journal	August 2017
Molecular Basis for Spirocycle Formation in the Paraherquamide Biosynthetic Pathway Fraley, Amy E.; Caddell Haatveit, Kersti; Ye, Ying Journal of the American Chemical Society, Vol. 142, Issue 5 https://doi.org/10.1021/jacs.9b09070	journal	January 2020
Novel Procedure for Modeling Ligand/Receptor Induced Fit Effects Sherman, Woody; Day, Tyler; Jacobson, Matthew P. Journal of Medicinal Chemistry, Vol. 49, Issue 2 https://doi.org/10.1021/jm050540c	journal	January 2006
Shornephine A: Structure, Chemical Stability, and P-Glycoprotein Inhibitory Properties of a Rare Diketomorpholine from an Australian Marine-Derived Aspergillus sp. Khalil, Zeinab G.; Huang, Xiao-cong; Raju, Ritesh The Journal of Organic Chemistry, Vol. 79, Issue 18 https://doi.org/10.1021/jo501501z	journal	September 2014
Biomimetic Total Synthesis of Malbrancheamide and Malbrancheamide B Miller, Kenneth A.; Welch, Timothy R.; Greshock, Thomas J. The Journal of Organic Chemistry, Vol. 73, Issue 8 https://doi.org/10.1021/jo800116y	journal	March 2008
Roquefortine E, a Diketopiperazine from an Australian Isolate of Gymnoascus reessii Clark, Ben; Capon, Robert J.; Lacey, Ernest Journal of Natural Products, Vol. 68, Issue 11 https://doi.org/10.1021/np0503101	journal	October 2005
Isolation of Talathermophilins from the Thermophilic Fungus Talaromyces thermophilus YM3-4 Guo, Ji-Peng; Tan, Jian-Lin; Wang, Yan-Li Journal of Natural Products, Vol. 74, Issue 10 https://doi.org/10.1021/np200365z	journal	October 2011
New Diketopiperazine Alkaloids from Penicillium fellutanum Kozlovsky, Anatoly G.; Vinokurova, Nataliya G.; Adanin, Vladimir M. Journal of Natural Products, Vol. 63, Issue 5 https://doi.org/10.1021/np9903853	journal	March 2000
Stereoselective Synthesis of Brevianamide E Zhao, Liang; May, Jonathan P.; Huang, Jack Organic Letters, Vol. 14, Issue 1 https://doi.org/10.1021/ol202880y	journal	November 2011
Structural basis for the promiscuous biosynthetic prenylation of aromatic natural products Kuzuyama, Tomohisa; Noel, Joseph P.; Richard, Stéphane B. Nature, Vol. 435, Issue 7044 https://doi.org/10.1038/nature03668	journal	June 2005
Multidimensional steric parameters in the analysis of asymmetric catalytic reactions Harper, Kaid C.; Bess, Elizabeth N.; Sigman, Matthew S. Nature Chemistry, Vol. 4, Issue 5 https://doi.org/10.1038/nchem.1297	journal	March 2012
Distinct mechanisms for spiro-carbon formation reveal biosynthetic pathway crosstalk Tsunematsu, Yuta; Ishikawa, Noriyasu; Wakana, Daigo Nature Chemical Biology, Vol. 9, Issue 12 https://doi.org/10.1038/nchembio.1366	journal	October 2013
Molecular insights into the enzyme promiscuity of an aromatic prenyltransferase Chen, Ridao; Gao, Bingquan; Liu, Xiao Nature Chemical Biology, Vol. 13, Issue 2 https://doi.org/10.1038/nchembio.2263	journal	December 2016
Fungal indole alkaloid biogenesis through evolution of a bifunctional reductase/Diels–Alderase Dan, Qingyun; Newmister, Sean A.; Klas, Kimberly R. Nature Chemistry, Vol. 11, Issue 11 https://doi.org/10.1038/s41557-019-0326-6	journal	September 2019
Fungal-derived brevianamide assembly by a stereoselective semipinacolase Ye, Ying; Du, Lei; Zhang, Xingwang Nature Catalysis, Vol. 3, Issue 6 https://doi.org/10.1038/s41929-020-0454-9	journal	May 2020
Prenylated indole derivatives from fungi: structure diversity, biological activities, biosynthesis and chemoenzymatic synthesis Li, Shu-Ming Nat. Prod. Rep., Vol. 27, Issue 1 https://doi.org/10.1039/B909987P	journal	January 2010
Isolation and structure (X-ray analysis) of marcfortine A, a new alkaloid from Penicillium roqueforti Polonsky, Judith; Merrien, Marie-Annick; Prangé, Thierry J. Chem. Soc., Chem. Commun., Issue 13 https://doi.org/10.1039/C39800000601	journal	January 1980
Predictive and mechanistic multivariate linear regression models for reaction development Santiago, Celine B.; Guo, Jing-Yao; Sigman, Matthew S. Chemical Science, Vol. 9, Issue 9 https://doi.org/10.1039/C7SC04679K	journal	January 2018
Total synthesis of (−)-penicimutanin a and related congeners Yu, Haiyong; Zong, Yan; Xu, Tao Chemical Science, Vol. 11, Issue 3 https://doi.org/10.1039/C9SC05252F	journal	January 2020
Comparative analysis of the biosynthetic systems for fungal bicyclo[2.2.2]diazaoctane indole alkaloids: the (+)/(−)-notoamide, paraherquamide and malbrancheamide pathways Li, Shengying; Srinivasan, Krithika; Tran, Hong MedChemComm, Vol. 3, Issue 8 https://doi.org/10.1039/c2md20029e	journal	January 2012
The structure of dimethylallyl tryptophan synthase reveals a common architecture of aromatic prenyltransferases in fungi and bacteria Metzger, U.; Schall, C.; Zocher, G. Proceedings of the National Academy of Sciences, Vol. 106, Issue 34 https://doi.org/10.1073/pnas.0904897106	journal	August 2009
Reversal of anticancer multidrug resistance by the ardeemins Chou, Ting-Chao; Depew, Kristopher M.; Zheng, Yu-Huang Proceedings of the National Academy of Sciences, Vol. 95, Issue 14 https://doi.org/10.1073/pnas.95.14.8369	journal	July 1998
Indole diketopiperazine alkaloids from the deep-sea-derived fungus Aspergillus sp. FS445 Liu, Zhaoming; Chen, Yuchan; Li, Saini Natural Product Research, Vol. 36, Issue 20 https://doi.org/10.1080/14786419.2021.1925271	journal	May 2021
Enzyme evolution in fungal indole alkaloid biosynthesis Fraley, Amy E.; Sherman, David H. The FEBS Journal, Vol. 287, Issue 7 https://doi.org/10.1111/febs.15270	journal	April 2020
Use of an Induced Fit Receptor Structure in Virtual Screening Sherman, Woody; Beard, Hege S.; Farid, Ramy Chemical Biology Drug Design, Vol. 67, Issue 1 https://doi.org/10.1111/j.1747-0285.2005.00327.x	journal	January 2006
Evolutionary Relationships of Microbial Aromatic Prenyltransferases Bonitz, Tobias; Alva, Vikram; Saleh, Orwah PLoS ONE, Vol. 6, Issue 11 https://doi.org/10.1371/journal.pone.0027336	journal	November 2011
Eurotiumins A–E, Five New Alkaloids from the Marine-Derived Fungus Eurotium sp. SCSIO F452 Zhong, Wei-Mao; Wang, Jun-Feng; Shi, Xue-Feng Marine Drugs, Vol. 16, Issue 4 https://doi.org/10.3390/md16040136	journal	April 2018
A New Prenylated Indole Diketopiperazine Alkaloid from Eurotium cristatum Zou, Xianwei; Li, Ying; Zhang, Xiaona Molecules, Vol. 19, Issue 11 https://doi.org/10.3390/molecules191117839	journal	November 2014
Prenylation of Aromatic Secondary Metabolites: A New Frontier for Development of Novel Drugs Alhassan, Am; Abdullahi, Mi; Uba, A. Tropical Journal of Pharmaceutical Research, Vol. 13, Issue 2 https://doi.org/10.4314/tjpr.v13i2.22	journal	February 2014
5-N-Acetylardeemin, a novel heterocyclic compound which reverses multiple drug resistance in tumor cells. II. Isolation and elucidation of the structure of 5-N-acetylardeemin and two congeners. Hochlowski, Jill E.; Mullally, Mark M.; Spanton, Stephen G. The Journal of Antibiotics, Vol. 46, Issue 3 https://doi.org/10.7164/antibiotics.46.380	journal	January 1993

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Data Science-Driven Analysis of Substrate-Permissive Diketopiperazine Reverse Prenyltransferase NotF: Applications in Protein Engineering and Cascade Biocatalytic Synthesis of (-)-Eurotiumin A

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