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University of Tuebingen
Auf der Morgenstelle 28
72076 Tuebingen, Germany



The Hughes Research Group specializes in microbial natural product discovery, synthesis, and chemical biology. We have characterized scores of natural products (NPs) using a combination of NMR spectroscopy and mass spectrometry, we have completed several total syntheses, and we have identified the cellular targets of numerous secondary metabolites.

We also develop derivatization strategies to discover new NPs in extracts. The method, called reactivity-guided isolation or chemical labeling, identifies metabolites based on their reactivity and has the potential to transform the way in which natural products chemists uncover certain classes of NPs. Specifically, the approach entails the covalent labeling of targeted NPs using chemoselective reagents or “probes” with prominent UV/vis properties and a distinct bromine or chlorine isotopic signature and is tied to the well-established practice of using reactive bromoarenes such as 4-bromobenzoyl chloride to yield crystalline material amenable to X-ray crystal structure analysis. Despite the fact that it does not directly furnish unaltered NPs, the method provides profound insight into the chemical space of an extract. It is a precise examination into the presence and abundance of a specific functionality or structural moiety that can be directly coupled to genome-mining studies. The method promises to de-orphan a large number of biosynthetic gene clusters and lead to the discovery of new NPs in a chemocentric manner.


To date, we have designed and applied probes that target NPs with electrophilic moieties (epoxides, α,β-unsaturated carbonyl groups, β-lactones, β-lactams), conjugated alkenes, terminal alkynes, enediynes, isocyanides, phosphonates, and amino groups.



Dr. Hughes was born and raised in bucolic western New York, USA. In 1999 he graduated with a B.S. in biochemistry and a minor in Latin from Geneseo College. In 2004 he completed a Ph.D. in chemistry from the University of California, Berkeley, with Prof. Dirk Trauner. Chambers was the first member of the then-nascent Trauner research group to earn a doctorate. Next, Dr. Hughes held an extended postdoctoral/research associate appointment with Prof. William Fenical at the Scripps Institution of Oceanography, UC San Diego. In 2012 Hughes was hired as assistant professor at Scripps. He then joined his family, in 2019, in Tübingen and is currently a Research Group Leader in the Department of Microbial Bioactive Compounds at the University of Tübingen.


1997–1999               Geneseo College (SUNY)
Research assistant

1999–2004               University of California, Berkeley    
Graduate student



2005–2012              Scripps Institution of Oceanography, UC San Diego
Postdoctoral scholar/Research associate IV

2012–2019              Scripps Institution of Oceanography, UC San Diego
Assistant Professor of Chemical Biology

2019–                      University of Tübingen
Research Group Leader

Foto-Kleinfeldt, Tübingen


phone: +49(0) 7071-2976989

E-bau 10th floor P07





Smith Babiaka, postdoctoral scholar

B.S., University of Buea, Cameroon

M.S., University of Buea, Cameroon

Ph.D., University of Buea, Cameroon




Shu-Ning Xia, Ph.D. student

B.E., Qilu University of Technology

M.E., Zhejiang University of Technology



Luca Salvi, Ph.D. student

B.S., University of Bologna

M.S., University of Bologna




Max Knab, Ph.D. student

B.S., Karlsruhe Institute of Technology

M.S., University of Tuebingen




Marita Wurm, technical assistant

Dipl. Biol., TU Kaiserslautern



Luca Schwenger, Hilfswissenschaftler

B.S., University of Konstanz




Giovanni Andrea Vitale, postdoctoral scholar

B.S., University of Naples "Federico II"

M.S., University of Naples "Federico II"

Ph.D., University of Campania "Luigi Vanvitelli"

postdoc, Stazione Zoologica Anton Dohrn




Annika Esch, Ph.D. student

B.A., University of Cambridge

M.S., University of Cambridge




Sehee Jang, Ph.D. student

B.S., Inha University

M.S., University of Tuebingen




Annika Schulz, technical assistant

B.S., Friedrich Schiller University Jena

M.S., Friedrich Schiller University Jena




Andreas Kulik, technical assistant

Dipl. Ing., Hochschule Reutlingen




Kiara, group mascot

Belgischer/Holländischer Schäferhund



(46) Castro‐Falcón G, Straetener J, Bornikoel J, Reimer D, Purdy TN, Berscheid A, Schempp FM, Liu DY, Linington RG, Brötz‐Oesterhelt H,* Hughes CC.* Antibacterial marinopyrroles and pseudilins act as protonophores. ACS Chem Biol. 2024;19:743-752.   doi:10.1021/acschembio.3c00773

(45) Nouioui I, Zimmermann A, Hennrich O, Xia S, Rössler O, Makitrynskyy R, Gomez-Escribano JP, Pötter G, Jando M, Döppner M, Wolf J, Neumann-Schaal M, Hughes C, Mast Y.* Challenging old microbiological treasures for natural compound biosynthesis capacity. Front Bioeng Biotechnol. 2024;12:1255151. doi:10.3389/fbioe.2024.1255151


(44) Moschny J, Daletos G, Proksch P, Hughes CC.* Structure elucidation of antibiotics. In: Sass P, ed. Antibiotics: Methods and Protocols, Methods in Molecular Biology. Vol 2601. 2nd ed. Humana Press Inc.; 2023. doi:10.1007/978-1-0716-2855-3_6

(43) Stincone P, Shah AKP, Schmid R, Graves L, Lambidis SP, Torres R, Xia SN, Minda V, Aron A, Wang M, Hughes CC, Petras D.* Evaluation of data dependent MS/MS acquisition parameters for non-targeted metabolomics and molecular networking of environmental samples: Focus on the Q Exactive platform. Anal Chem. 2023;95:12673-12682. doi:10.1021/acs.analchem.3c01202


(42) Wilkinson IVL, Castro‐Falcón G, Roda‐Serrat MC, Purdy TN, Straetener J, Brauny MM, Maier L, Brötz‐Oesterhelt H, Christensen LP, Sieber SA,* Hughes CC.* The cyanobacterial “nutraceutical” phycocyanobilin inhibits cysteine protease legumain. ChemBioChem. 2023;e202200455:1-10. doi:10.1002/cbic.202200455

(41) Zhang L, Esquembre LA, Xia SN, Oesterhelt F, Hughes CC,* Brötz-Oesterhelt H,* Teufel R.* Antibacterial synnepyrroles from human-associated Nocardiopsis sp. show protonophore activity and disrupt the bacterial cytoplasmic membrane. ACS Chem Biol. 2022;17:2836-2848. doi:10.1021/acschembio.2c00460

(40) Reher R, Aron AT, Fajtová P, Stincone P, Wagner B, Pérez-Lorente AI, Liu C, Shalom IYB, Bittremieux W, Wang M, Jeong K, Matos-Hernandez ML, Alexander KL, Caro-Diaz EJ, Naman CB, Scanlan JHW, Hochban PMM, Diederich WE, Molina-Santiago C, Romero D, Selim KA, Sass P, Brötz-Oesterhelt H, Hughes CC, Dorrestein PC, O’Donoghue AJ, Gerwick WH,* Petras D.* Native metabolomics identifies the rivulariapeptolide family of protease inhibitors. Nat Commun. 2022;13:1-12. doi:10.1038/s41467-022-32016-6

(39) Engelbrecht A, Wolf F, Esch A, Kulik A, Kozhushkov SI, de Meijere A, Hughes CC,* Kaysser L.* Discovery of a cryptic nitro intermediate in the biosynthesis of the 3-(trans-2′-aminocyclopropyl)alanine moiety of belactosin A. Org Lett. 2022;24:736-740. doi:10.1021/acs.orglett.1c04205

(38) Hughes CC.* Chemical labeling strategies for small molecule natural product detection and isolation. Nat Prod Rep. 2021;38:1684-1705. doi:10.1039/d0np00034e


(37) Förster C, Handrick V, Ding Y, Nakamura Y, Paetz C, Schneider B, Castro-Falcón G, Hughes CC, Luck K, Poosapati S, Kunert G, Huffaker A, Gershenzon J, Schmelz EA, Köllner TG.* Biosynthesis and antifungal activity of fungus-induced O-methylated flavonoids in maize. Plant Physiol. 2022;188:167-190. doi:10.1093/plphys/kiab496

(36) Tuttle RN, Rouse GW, Castro-Falcón G, Hughes CC, Jensen PR.* Specialized metabolite-mediated predation defense in the marine actinobacterium Salinispora. Appl Environ Microbiol. 2022;88:e01176-21. doi:10.1128/AEM.01176-21


(35) Ding Y, Murphy KM, Poretsky E, Mafu S, Yang B, Char SN, Christensen SA, Saldivar E, Wu M, Wang Q, Ji L, Schmitz RJ, Kremling KA, Buckler ES, Shen Z, Briggs SP, Bohlmann J, Sher A, Castro-Falcon G, Hughes CC, Huffaker A, Zerbe P, Schmelz EA.* Multiple genes recruited from hormone pathways partition maize diterpenoid defences. Nat Plants. 2019;5:1043-1056. doi:10.1038/s41477-019-0509-6

(34) Seiler GS, Hughes CC.* Progress toward the total synthesis of lymphostins: Preparation of a functionalized tetrahydropyrrolo[4,3,2-de]quinoline and unusual oxidative dimerization. J Org Chem. 2019;84:9339-9343. doi:10.1021/acs.joc.9b01041

(33) Moss NA, Seiler G, Leao TF, Castro-Falcon G, Gerwick L, Hughes CC, Gerwick WH.* Nature’s combinatorial biosynthesis produces vatiamides A–F. Angew Chem Int Ed. 2019;58:9027-9031. doi:10.1002/anie.201902571

(32) Kearney SE, Zahoránszky-Kohalmi G, Brimacombe KR, Henderson MJ, Lynch C, Zhao T, Wan KK, Itkin Z, Rohde JM,* et al. Canvass: A crowd-sourced, natural-product screening library for exploring biological space. ACS Cent Sci. 2018;4:1727-1741. doi:10.1021/acscentsci.8b00747

(31) Castro-Falcón G, Seiler G, Demir O, Rathinaswamy M, Hamelin D, Hoffmann RM, Makowski S, Letzel AC, Field S, Burke J, Amaro RE, Hughes CC.* Neolymphostin A is a covalent phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) dual inhibitor that employs an unusual electrophilic vinylogous ester. J Med Chem. 2018;61:10463-10472. doi:10.1021/acs.jmedchem.8b00975

(30) Castro-Falcón G, Millán-Aguiñaga N, Roullier C, Jensen PR, Hughes CC.* Nitrosopyridine probe to detect polyketide natural products with conjugated alkenes: Discovery of novodaryamide and nocarditriene. ACS Chem Biol. 2018;13:3097-3106. doi:10.1021/acschembio.8b00598

(29) Patin N V, Floros DJ, Hughes CC, Dorrestein PC, Jensen PR.* The role of inter-species interactions in Salinispora specialized metabolism. Microbiology. 2018;164:946-955. doi:10.1099/mic.0.000679

(28) Mafu S, Ding Y, Murphy KM, Yaacoobi O, Addison JB, Wang Q, Shen Z, Briggs SP, Bohlmann J, Castro-Falcon G, Hughes CC, Betsiashvili M, Huffaker A, Schmelz EA, Zerbe P.* Discovery, biosynthesis and stress-related accumulation of dolabradiene-derived defenses in maize. Plant Physiol. 2018;176:2677-2690. doi:10.1104/pp.17.01351

(27) Gallagher KA, Wanger G, Henderson J, Llorente M, Hughes CC, Jensen PR.* Ecological implications of hypoxia-triggered shifts in secondary metabolism. Environ Microbiol. 2017;19:2182-2191. doi:10.1111/1462-2920.13700

(26) Reimer D, Hughes CC.* Thiol-based probe for electrophilic natural products reveals that most of the ammosamides are artifacts. J Nat Prod. 2017;80:126-133. doi:10.1021/acs.jnatprod.6b00773

(25) Castro-Falcon G, Hahn D, Reimer D, Hughes CC.* Thiol probes to detect electrophilic natural products based on their mechanism of action. ACS Chem Biol. 2016;11:2328-2336. doi:10.1021/acschembio.5b00924

(24) Richter TKS, Hughes CC, Moore BS.* Sioxanthin, a novel glycosylated carotenoid, reveals an unusual subclustered biosynthetic pathway. Environ Microbiol. 2015;17:2158-2171. doi:10.1111/1462-2920.12669

(23) Álvarez-Micõ X, Jensen PR, Fenical W, Hughes CC.* Chlorizidine, a cytotoxic 5H-pyrrolo[2,1-a]isoindol-5-one-containing alkaloid from a marine Streptomyces sp. Org Lett. 2013;15:988-991. doi:10.1021/ol303374e

(22) Yamanaka K, Ryan KS, Gulder TAM, Hughes CC, Moore BS.* Flavoenzyme-catalyzed atropo-selective N,C-bipyrrole homocoupling in marinopyrrole biosynthesis. J Am Chem Soc. 2012;134:12434-12437. doi:10.1021/ja305670f


(21) Yang M, Liu Z, Hughes CC, Stern AM, Wang H, Zhong Z, Kan B, Fenical W, Zhu J. Bile salt-induced intermolecular disulfide bond formation activates Vibrio cholerae virulence. Proc Natl Acad Sci. 2013;110:2348-2353.

(20) Haste NM, Hughes CC, Tran DN, Fenical W, Jensen PR, Nizet V, Hensler ME. Pharmacological properties of the marine natural product marinopyrrole A against methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother. 2011;55:3305-3312.

(19) Hughes CC, Fenical W. Antibacterials from the sea. Chem - A Eur J. 2010;16:12512-12525.

(18) Pangerl M, Hughes CC, Trauner D. Total synthesis of newbouldine via reductive N–N bond formation. Tetrahedron. 2010;66:6626-6631.

(17) Hughes CC, Fenical W. Total synthesis of the ammosamides. J Am Chem Soc. 2010;132:2528-2529.

(16) Hughes CC, Kauffman CA, Jensen PR, Fenical W. Structures, reactivities, and antibiotic properties of the marinopyrroles A−F. J Org Chem. 2010;75:3240-3250.

(15) Hughes CC, Yang YL, Liu WT, Dorrestein PC, La Clair JJ, Fenical W. Marinopyrrole A target elucidation by acyl dye transfer. J Am Chem Soc. 2009;131:12094-12096.

(14) Nett M, Gulder TAM, Kale AJ, Hughes CC, Moore BS. Function-oriented biosynthesis of β-lactone proteasome inhibitors in Salinispora tropica. J Med Chem. 2009;52:6163-6167.

(13) Hughes CC, MacMillan JB, Gaudêncio SP, Fenical W, La Clair JJ. Ammosamides A and B target myosin. Angew Chemie - Int Ed. 2009;48:728-732.

(12) Hughes CC, MacMillan JB, Gaudêncio SP, Jensen PR, Fenical W. The ammosamides: structures of cell cycle modulators from a marine-derived Streptomyces species. Angew Chemie - Int Ed. 2009;48:725-727.

(11) Hughes CC, Prieto-Davo A, Jensen PR, Fenical W. The marinopyrroles, antibiotics of an unprecedented structure class from a marine Streptomyces sp. Org Lett. 2008;10:629-631.

(10) Miller AK, Hughes CC, Kennedy-Smith JJ, Gradl SN, Trauner D. Total synthesis of (−)-heptemerone B and (−)-guanacastepene E. J Am Chem Soc. 2006;128:17057-17062.

(9) Endicott CA, Strauss HL, Hughes CC, Trauner D. Infrared hole burning and conformational change in a borane-ammonia complex. J Phys Chem A. 2005;109:7714-7717.


(8) Bowie AL, Hughes CC, Trauner D. Concise synthesis of (±)-rhazinilam through direct coupling. Org Lett. 2005;7:5207-5209.

(7) Hughes CC, Miller AK, Trauner D. An electrochemical approach to the guanacastepenes. Org Lett. 2005;7:3425-3428.

(6) Hughes CC, Trauner D. Palladium-catalyzed couplings to nucleophilic heteroarenes: The total synthesis of (−)-frondosin B. Tetrahedron. 2004;60:9675-9686.

(5) Hughes CC, Kennedy-Smith JJ, Trauner D. Synthetic studies toward the guanacastepenes. Org Lett. 2003;5:4113-4115.

(4) Johnson DK, Schillinger KJ, Kwait DM, Hughes CC, McNamara EJ, Ishmael F, O’Donnell RW, Chang MM, Hogg MG, Dordick JS, Santhanam L, Ziegler LM, Holland JA. Inhibition of NADPH oxidase activation in endothelial cells by ortho-methoxy-substituted catechols. Endothelium. 2002;9:191-203.

(3) Hughes CC, Scharn D, Mulzer J, Trauner D. Borane-ammonia complexes stabilized by hydrogen bonding. Org Lett. 2002;4:4109-4111.

(2) Hughes CC, Trauner D. Concise total synthesis of (−)-frondosin B using a novel palladium-catalyzed cyclization. Angew Chemie - Int Ed. 2002;41:1569-1572.

(1) Hughes CC, Trauner D. The total synthesis of (−)-amathaspiramide F. Angew Chemie - Int Ed. 2002;41:4556-4559.



Hughes Research Group

Interfaculty Institute for Microbiology and Infection Medicine

University of Tübingen

Auf der Morgenstelle 28

72076 Tübingen Deutschland

Chambers C. Hughes, Ph.D.


phone: +49(0) 7071-2976989

E-bau 10th floor P07

Ph.D. positions available

send via email:

CV, motivation letter, references, transcripts

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