The main research projects being pursued by Philip Proteau's laboratory involve various aspects of the chemistry and biology of natrual products. All of these projects are collaborative in nature. One project is aimed at the discovery of novel bioactive compounds from Indonesian soil bacteria and a second focuses on the syntesis of the antiproliferative agent coibamide A. These projects incorporate a blend of natural products chemistry, organic sythesis, and spectroscopy.
A key effort is a joint project with Drs. Zabriskie and Mahmud in collaboration with Dr. Dwi Andreas Santosa from the Indonesian Center for Biodiversity and Biotechnology. Dr. Santosa has isolated numerous novel actinomycetes (soil bacteria) from the unique Black Water Ecosystem in Kalimantan, Indonesia and we at OSU culture these bacteria and screen their extracts for biological activity, mainly focusing on antibiotic action. Active extracts are then subjected to factionation and ultimately isolation and structure elucidation of the active components. Compounds with potential antitumor activity are further explored for mechanism of action by our pharmacology colleague, Dr. Jane Ishmael.
The second project is in collaboration with Dr. McPhail and Dr. Ishmael. Dr. McPhail's group isolated coibamide A several years ago from a cyanobacterial assemblage collected off the coast of Panama. Inconsistent natural supplies and challenges in culturing the producing organism have necessitated a synthetic route to this highly N-methylated cyclic depsipeptide natural product. In addition to targeting the natural product, we are also working on the synthesis of analogs to address structure-activity relationships. Dr. Ishmael and her students have been studying the molecular mechanism of action of coibamide and also test the synthetic compounds.
Sheng, Y.; Fotso, S.; Serrill, J.D.; Shahab, S.; Santosa, D.A.; Ishmael, J.E.; Proteau, P.J.; Zabriskie, T.M.; Mahmud, T. “Succinylated Apoptolidins from Amycolatopsis sp. ICBB 8242” Org. Lett. 2015, 17, 2526–2529. DOI: 10.1021/acs.orglett.5b01055
Vining, O.B.; Medina, R.A; Mitchell, E.A.; Videau, P.; Li, D.; Serrill, J.D.; Kelly, J.X.; Gerwick, W.H.; Proteau, P.J.; Ishmael, J.E.; McPhail, K.L. “Depsipeptide Companeramides from a Panamanian Marine Cyanobacterium Associated with the Coibamide Producer” J. Nat. Prod. 2015, 78, 413-420.
Serrill, J.D.; Tan, M.; Fotso, S.; Sikorska, J.; Kasanah, N.; Hau, A.M.; McPhail, K.L.; Zabriskie, T.M.; Mahmud, T.; Proteau, P.J.; Ishmael, J.E. “Apoptolidins A and C Activate AMPK in Metabolically Sensitive Cell Types and Are Mechanistically Distinct from Oligomycin A” Biochem. Pharmacol. 2015, 93, 251-265.
Hau, A.M.; Greenwood, J.A.; Löhr, C.V.; Serrill, J.D.; Proteau, P.J.; Ganley, I.G.; McPhail, K.L.; Ishmael, J.E. “Coibamide A induces mTOR-independent autophagy and cell death in human glioblastoma cells,” PLoS One 2013, 8(6):e65250.
Choi, H.; Proteau, P.J.; Byrum, T.; Pereira, A.R.; Gerwick, W.H. “Cymatherelactone and Cymatherols A-C, Polycyclic Oxylipins from the Marine Brown Alga Cymathere triplicata,” Phytochemistry 2012, 73, 134-141.
Sloat, B.R.; Sandoval, M.A.; Li, D.; Chung, W.G.; Lansakara-P, D.S.; Proteau, P.J.; Kiguchi, K.; Digiovanni, J.; Cui, Z. “In vitro and in vivo anti-tumor activities of a gemcitabine derivative carried by nanoparticles.” Int. J. Pharm. 2011, 409, 278-288.
Fotso, S.; Santosa, D.A.; Saraswati, R.; Yang, J.; Mahmud, T.; Zabriskie, T.M.; Proteau, P.J. “Modified Phenazines from an Indonesian Streptomyces sp.” J. Nat. Prod. 2010, 73, 472-475. doi: 10.1021/np9005647.
Sorrels, C.M.; Proteau, P.J.; Gerwick, W.H. “Organization, evolution, and expression analysis of the biosynthetic gene cluster for scytonemin, a cyanobacterial UV-absorbing pigment.” Appl. Environ. Microbiol. 2009, 75, 4861-4869.
Fotso, S.; Mark Zabriskie, T.M.; Proteau, P.J.; Flatt, P.M.; Santosa, D.A.; Sulastri, and Mahmud, T. “Limazepines A-F, Pyrrolo[1,4]Benzodiazepine Antibiotics from an Indonesian Micrococcus sp.” J. Nat. Prod, 2009, 72, 690-695.