BJ smiles at camera in front of a brick wall

Dr. Philmus, an Associate Professor, has been researching natural products since his doctoral research at the University of Hawaiʻi. His research focused on isolating and characterizing natural products from cyanobacteria using NMR spectroscopy, mass spectrometry, and chemical synthesis. He then shifted his focus to biosynthesis, using precursor labeling, heterologous expression, and in vitro reconstitution. After a postdoctoral position at Texas A&M University, Dr. Philmus delved into complex biosynthetic mechanisms, including the biosynthesis of the cofactor F0. He learned to handle radical SAM enzymes, which are challenging due to their oxygen sensitivity, and in vitro NMR monitoring of enzymatic reactions and kinetics.

Publications

The Philmus lab is interested in specialized metabolites produced by microorganisms.

We love natural products/specialized metabolites, especially from microorganisms. Our multidisciplinary research program involves genome mining and bioinformatic tool development, machine learning, natural products chemistry, molecular biology, protein biochemistry and more recently collaborations on how to adapt microfluidics for natural products and drug discovery research.

A scientific diagram showing the biosynthetic pathway of lyngbyatoxin A production. The image consists of three parts connected by arrows from left to right: 1) A circular plasmid labeled "ltx gene cluster" with small red and blue segments, 2) A stylized representation of Anabaena sp. strain PCC 7120 shown as a chain of light blue-green cylindrical cells, and 3) The chemical structure of lyngbyatoxin A, depicted as a complex organic molecule with multiple rings and functional groups. The diagram illustrates

Our initial explorations have focused on specialized metabolites from cyanobacteria including synthetic biology for cyanobacterial drug discovery. More recently we have begun working with rare actinobacteria. We are also investigating the biochemical mechanisms that organisms use to form some of the impressive structures found in natural products.

Students that join the Philmus lab will learn a variety of techniques including microbiology, molecular biology, protein biochemistry, analytical chemistry, and machine learning.

Current Members

Kyle Axt 

Ph.D. candidate, Pharmaceutical Sciences 

Kyle joined the Philmus lab in Spring 2022 and is currently a 4th year Ph.D. candidate. Kyle is interested in merging computational biology and natural products research. He is developing machine learning methods and new computational algorithms to help link natural products and their biosynthetic gene clusters. In support of this, he is also developing a cell-free expression assay for the high-throughput characterization of adenylation domains to enable better predictions of encoded natural products.

Shaz Sutherland 

Ph.D. candidate, Pharmaceutical Sciences

Shaz joined the lab in Spring 2024 and is currently a 2nd year Ph.D. candidate. Shaz is interested in dissection and characterization of the biosynthesis of the anti-infective kibdelomycin and developing synthetic biology chassis to enable medicinal chemistry efforts.

Vitoria Mingola Da Silva

Undergraduate student, Biochemistry & Molecular Biology

Vitoria joined the lab in Winter of 2024 and showed a keen interest in working with cell-free expression technology. She has been involved in developing and using cell-free expression technology to enable the high-throughput characterization of adenylation domains.

News

4/5/2022 - Congratulations to Jessee for being awarded the Bioengineering travel award!!! Congratulations Jessee!

1/30/2022 - Daniel's first paper is officially online and published in the Journal of Natural Products. LINK

7/21/2021 - Daniel's first paper on the development of a RuAAC coupled to LC-MS/MS methodology for the identification of alkyne containing natural products is up online as a pre-print at ChemRXiv (Here). Look for the official paper soon. Congratulations Daniel!

7/17/2021 - Congratulations to Jessee for receiving an acceptance of their first, first-author paper in Synthetic Biology (Open Access article). Congratulations Jessee and Brenda! LINK

6/15/2021 - Congratulations to Daniel on passing his Ph.D. preliminary exam!!! Some exciting research awaits us.

6/7/2021 - Congratulations to Jessee on passing their Ph.D. preliminary exam!!! Excited to continue pushing forward of their research projects.

5/20/2021 - Congratulations to Savannah for expertly navigating her Honor's thesis defense! Look for the paper soon!

10/28/2020 -  Our collaborative paper with the Megraw lab on vinca alkaloids in C. roseus has been published in Plant Direct!! Thanks to Val and Molly for the wonderful collaboration.

12/6/2019 - Our Joint Genome Institute DNA Synthesis proposal focusing on 1,2,4-triazine secondary metabolites was approved!!! We are excited to build on our collaboration with JGI and push this research area forward.

9/15/2019 - Daniel officially joined the Philmus lab.

7/22/2019 - Dr. Philmus was selected to give a presentation at the Enzymes, cofactors and metabolic pathways GRC meeting. Thank you to all the lab members and collaborators that made the research possible.

7/15/2019 - Dr. Philmus was selected to give a presentation at the American Society of Pharmacognosy annual meeting in Madison, WI. Thank you to all the lab members and collaborators that made the research possible.

6/24/2019 - Savannah joined the Philmus lab and was awarded a Summer Undergraduate Research Scholarship from the College of Pharmacy. Welcome and Congratulations Savannah!!!

5/27/2019 - Daniel joined the Philmus lab as a rotation student. Welcome Daniel!!

4/1/2019 - Jessee joined the Philmus lab. Welcome Jessee!!!

8/9/2018 - Congratulations to Khaled and Linh on having their paper entitled " Self-resistance of natural product producers: Past, present and future focusing on self-resistant protein variants" recognized as one of the top 20 papers read from ACS Chemical Biology for the second straight month!!!! Way to go guys!! Journal link

7/13/2018 - Congratulations to Khaled and Linh on having their paper entitled " Self-resistance of natural product producers: Past, present and future focusing on self-resistant protein variants" recognized as one of the top 20 papers read from ACS Chemical Biology!!!!

7/5/2018 - Congratulations to Kaitlyn for being the lead author entitled "The influence of sigma factors and ribosomal recognition elements on heterologous expression of cyanobacterial gene clusters in Escherichia coli" that was accepted for publication in FEMS Microbiology Letters. Congratulations everyone!!!!

6/25/2018 - Brenda has officially joined the lab as a Ph.D. candidate. Welcome Brenda.

6/25/2018 - James has joined the lab as a rotation student. Welcome James.

5/25/2018 - Khaled has recently joined the startup company, Gadusol Laboratories, Inc. Congratulations and good luck Khaled!!!!

Publications

From Oregon State University (Corresponding author in bold)

  1. Back, D.; Shaffer, B.; Loper, J.; Philmus, B. Untargeted identification of alkyne containing natural products using ruthenium catalyzed azide alkyne cycloaddition reactions coupled to LC-MS/MS. Journal of Natural Products, 2022, 85(1), 105-114. doi: 10.1021/acs.jnatprod.1c00798.
  2. Svoboda, J.; Cisneros, B.; Philmus, B. Evaluation of inducible promoter-riboswitch constructs for heterologous protein expression in cyanobacterial species Anabaena sp. PCC 7120. Synthetic Biology, 2021, ysab019. doi: 10.1093/synbio/ysab019
  3. Rodrigues, R. R.; Gurung, M.; Li, Z.; García-Jaramillo, M.; Greer, R.; Bauchinger, F.; You, H.; Pederson, J. W.; Gaulke, C.; Vasquez-Perez, S.; White, K. D.; Frink, B.; Philmus, B.; Jump, D. B.; Trinchieri, G.; Berry, D.; Sharpton, T. J.; Dzutsev, A.; Morgun, A.; Shulzhenko, N. Transkingdom interactions between Lactobacilli and hepatic mitochondria attenuate western diet induced diabetes. Nature Communications, 2020, 12(1):101.  doi: 10.1038/s41467-020-20313-x.
  4. Fraser, V.; Philmus, B. Megraw, M. Plant Direct., 2020, 4(9), e00267. doi: 10.1002/pld3.267. Metabolomics analysis reveals both plant variety and choice of hormone treatment modulate vinca alkaloid production in Catharanthus roseus.
  5. Videau, P.; Wells, K. N.; Singh, A. J.; Eiting, J.; Proteau, P. J.; Philmus, B. ACS Synth. Biol. 2020, 9(1), 63-75. doi: 10.1021/acssynbio.9b00334. Expanding the natural products heterologous expression repertoire in the model cyanobacterium Anabaena sp. strain PCC 7120: Production of pendolmycin and teleocidin B-4.
  6. Nofiani, R.; Philmus, B.; Nindita, Y.; Mahmud, T.Medchemcomm. 2019, 10, 1517-1530. doi: 10.1039/c9md00162j 3-Ketoacyl-ACP synthase (KAS) III homologues and their roles in natural product biosynthesis.
  7. Wells, K. N.; Videau, P.; Philmus, B. FEMS Microbiol. Lett. 2018, 365, doi: 10.1093/femsle/fny164. The influence of sigma factors and ribosomal recognition elements on heterologous expression of cyanobacterial gene clusters in Escherichia coli.
  8. Gallegos, D.; Saurí, J.; Cohen, R.; Wan, X.; Videau, P.; Vallota-Eastman, A.; Shaala, L.; Youssef, D.; Williamson, R. T.; Martin, G.; Philmus, B.; Sikora, A.; Ishmael, J.; McPhail, K. J. Nat. Prod. 2018, 81, 1417-1425. doi: 10.1021/acs.jnatprod.8b00117. Jizanpeptins, cyanobacterial protease inhibitors from a Symploca sp. cyanobacterium collected in the Red Sea.
  9. Almabruk, K. H.; Dinh, L. K.; Philmus, B. ACS Chem. Biol. 2018, 13, 1426-1437. doi: 10.1021/acschembio.8b0017 Self-resistance of natural product producers: Past, present and future focusing on self-resistant protein variants.
  10. Videau, P.; Rivers, O. S.; Tom, S. K.; Oshiro, R. T.; Ushijima, B.; Swenson, V. A.; Philmus, B.; Gaylor, M. O.; Cozy, L. M. Molec. Microbiol. 2018, in press, doi: 10.1111/mmi.13974. The hetZ gene indirectly regulates heterocyst development at the level of pattern formation in Anabaena sp. strain PCC 7120.
  11. Yan, Q.; Lopes, L. D.; Shaffer, B. T.; Kidarsa, T. A.; Vining, O.; Philmus, B.; Song, C.; Stockwell, V. O.; Raaijmakers, J. M.; McPhail, K. L.; Andreote, F. D.; Chang, J. H.; Loper, J. E. MBio. 2018; 9, pii: e01845-17. doi: 10.1128/mBio.01845-17. Secondary metabolism and interspecific competition affect accumulation of spontaneous mutants in the GacS-GacA regulatory system in Pseudomonas protegens.
  12. Fenwick, M. K.; Almabruk, K. H.; Ealick, S. E.; Begley, T. P.; Philmus, B. Biochemistry 2017; 56, 3934-3944. Biochemical characterization and structural basis of reactivity and regioselectivity differences between Burkholderia thailandensis and Burkholderia glumae 1,6-didesmethyltoxoflavin N-methyltransferase.
  13. Alanjary, M.; Kronmiller, B.; Adamek, M.; Blin, K.; Weber, T.; Huson, D.; Philmus, B.; Ziemert, N. Nucleic Acids Research, 2017, doi: 10.1093/nar/gkx360. The Antibiotic Resistant Target Seeker (ARTS), an exploration engine for antibiotic cluster prioritization and novel drug target discovery.
  14. Yan, Q.; Philmus, B.; Chang, J. H.; Loper, J. E. Elife. 2017 6, pii: e22835. doi: 10.7554/eLife.22835. Novel mechanism of metabolic co-regulation coordinates the biosynthesis of secondary metabolites in Pseudomonas protegens.
  15. Abugrain, M. E.; Brumsted, C. J.; Osborn, A. R.; Philmus, B.; Mahmud, T. ACS Chem. Biol. 2017, 12, 362-366. A highly promiscuous ß-Ketoacyl-ACP synthase (KAS) III-like protein is involved in pactamycin biosynthesis.
  16. Videau, P.; Wells, K. N.; Singh, A. K.; Gerwick, W. H.; Philmus, B. ACS Synth. Biol., 2016, 5(9), 978-988. Assessment of Anabaena sp. strain PCC 7120 as a heterologous expression host for cyanobacterial natural products: Production of lyngbyatoxin A.
  17. Yan, Q.; Philmus, B.; Hesse, C.; Kohen, M.; Chang, J. H.; Loper, J. E. Front. Microbiol. 2016, 19(7), 497, The rare codon AGA is involved in regulation of pyoluteorin biosynthesis in Pseudomonas protegens Pf-5.
  18. Naurin, S.; Bennett, J.; Videau, P.; Philmus, B.; Soule, T. J. Phycol. 2016, 52(4), 564-571. The response regulator npun_f1278 is essential for scytonemin biosynthesis in the cyanobacterium Nostoc punctiforme ATCC 29133.
  19. Videau, P.; Rivers, O. S.; Ushijima, B.; Oshiro, R. T.; Kim, M. J.; Philmus, B.; Cozy, L. M. Mutation of the murC and murB genes impairs heterocyst differentiation in Anabaena sp. strain PCC 7120.
  20. Philmus, B.; Shaffer, B. T.; Kidarsa, T. A.; Yan, Q.; Raaijmakers, J. M.; Begley, T. P.; Loper, J. E. ChemBioChem 2015, 16(12), 1782-1790.Investigations into the biosynthesis, regulation and self-resistance of toxoflavin in Pseudomonas protegens Pf-5.

As a postdoctoral researcher

  1. Fenwick, M. K.; Philmus, B.; Begley, T. P.; Ealick, S. E. Biochemistry. 2016, 55(19), 2748-2759. Burkholderia glumae ToxA is a dual specificity methyltransferase that catalyzes the last two steps of toxoflavin biosynthesis.
  2. Xu, H.; Chakrabarty, Y.; Philmus, B.; Mehta, A. P.; Bhandari, D.; Hohmann, H-P.; Begley, T. P. J. Biol Chem. 2016, 291, 23506-23515, Identification of the first riboflavin catabolic gene cluster isolated from Microbacterium maritypicum G10.
  3. Philmus, B.; Decamps, L.; Berteau, O.; Begley, T.P. Biosynthetic versatility and coordinated action of 5’-deoxyadenosyl radicals in deazaflavin biosynthesis. J. Am. Chem. Soc. 2015, 137(16), 5406-5413.
  4. Mehta, A. P.; Abdelwahed, S.; Mahanta, N.; Fedoseyenko, D.; Philmus, B.; Cooper, L.; Liu, Y.; Jhulki, I.; Ealick, S. E.; Begley, T. P. Radical SAM Enzymes in cofactor biosynthesis: a treasure trove of complex organic radical rearrangement reactions J. Biol. Chem., 2014, 290, 3980-3986.
  5. Decamps, L.; Philmus, B.; Benjdia, A.; White, R.; Begley, T. P.; Berteau, O. Biosynthesis of F0, precursor of the F420 cofactor, requires a unique two radical-SAM domain enzyme and tyrosine as substrate. J. Am. Chem. Soc., 2012, 134 (44), 18173-18176.
  6. Philmus, B., Abdelwahed, S.; Williams, H. J.; Fenwick, M. K.; Ealick, S. E.; Begley, T. P. Identification of the product of toxoflavin lyase: degradation via a Baeyer-Villiger oxidation. J. Am. Chem. Soc., 2012, 134, 5326-5330.
  7. Lai, R. Y.; Huang, S.; Fenwick, M. K.; Hazra, A.; Zhang, Y.; Rajashankar, K.; Philmus, B.; Kinsland, C.; Sanders, J. M.; Ealick, S. E.; Begley, T. P.Thiamin pyrimidine biosynthesis in Candida albicans : a remarkable reaction between histidine and pyridoxal phosphate. J. Am. Chem. Soc., 2012, 134 (22), 9157-9159.
  8. Fenwick, M. K.; Philmus, B.; Begley, T. P.; Ealick, S. E.Toxoflavin lyase requires a novel 1-His-2-carboxylate facial triad. Biochemistry, 2011, 50, 1091-1100.
  9. Greenwald, J. W.; Greenwald, C. J.; Philmus, B. J.; Begley, T. P.; Gross, D. C. RNA-seq analysis reveals that an ECF σ factor, AcsS, regulates achromobactin biosynthesis in Pseudomonas syringae pv. syringae B728a. PLoS One, 2012, 7, e34804.
  10. Pribat, A.; Blaby, I. K.; Lara-Núñez, A.; Jeanguenin, L.; Fouquet, R.; Frelin, O.; Gregory, J. F.; Philmus, B.; Begley, T. P.; de Crécy-Lagard, V.; Hanson, A. D. A 5-formyltetrahydrofolate cycloligase paralog from all domains of life: comparative genomic and experimental evidence for a cryptic role in thiamin metabolism. Funct. Integr. Genomics, 2011, 11, 467-478.

As a graduate student

  1. Christiansen, G.; Philmus, B.; Hemscheidt, T.; Kurmayer, R. Genetic variation of adenylation domains of the anabaenopeptin synthesis operon and evolution of substrate promiscuity. J. Bacteriol., 2011, 193, 3822-3831.
  2. Philmus, B; Guerrette, J. P.; Hemscheidt, T. K.Substrate specificity and scope of MvdD, a GRASP-like ligase from the microviridin biosynthetic gene cluster. ACS Chem Biol., 2009, 4, 429-434.
  3. Okumura, H.; Philmus, B.; Portmann, C.; Hemscheidt, T. Homotyrosine containing cyanopeptolins K and L and anabaenopeptins 908 and 915 from Planktothrix agardhii 126/8. J. Nat. Prod. 2009, 72, 172-1766.
  4. Philmus, B.; Christiansen, G.; Yoshida, W.; Hemscheidt, T. Posttranslational modifications during microviridin biosynthesis. ChemBioChem, 2008, 9, 3066-3073.
  5. Christiansen,G.; Molitor, C.; Philmus, B.; Kurmayer, R. Nontoxic strains of cyanobacteria are the result of major gene deletion events induced by a transposable element. Molec. Biol. Evol., 2008, 25, 1695 - 1704.