EDUCATION:

Ph.D. Johns Hopkins University Baltimore MD, 2011
Chemistry, (Adviser, Prof. Craig A. Townsend)

Michigan State University, East Lansing, MI, 2005
Chemistry

CONTACT INFORMATION:

Email …… rmphelan@lbl.gov
Phone ….. 8109238844
Office …… 4141-F
Bench ….. 4550-42
Address

5885 Hollis Street, 4th Floor, Emeryville, CA 94608

Current Research

Study and Engineering of Polyketide Synthases for the Production of Replacement Petrochemicals.

  • Poust, S.; Phelan, R. M.; Deng, K.; Katz, L.; Petzold, C.; Keasling, J. D. “Divergent Mechanistic Routes for gem-Dimethyl Group Formation in Complex Polyketide Biosynthesis” Angew. Chem. Int. Ed. Engl. 2015, 54, 2370-2373
  • Barajas, J.*; Phelan, R. M.*; Schaub, A. J.; Kleiwer, J. T.; Luo, R.; Kelly, P. J.; Keasling, J. D.; Tsai, S.-C. “Comprehensive Structural and Biochemical Analysis of the Terminal Myxalamid Reductase Domain for the Engineered Production of Highly Reduced Alcohols” Chem. Biol, 2015, 22, 1018-1029
    *Denotes equal contribution

 

Development of next-generation tools for the rapid metabolic engineering of Streptomyces venezuelae

Due to the rich history of Streptomyces as prolific producers of natural products, this genus of bacteria has recently garnered attention for its potential in synthetic biology. However, the dearth of genetic tools available to control and monitor protein expression precludes rapid and predictable metabolic engineering that is possible in hosts such as Escherichia coli or Saccharomyces cerevisiae. In an effort to improve genetic tools for Streptomyces venezuelae, we developed an improved method to monitor protein expression in intact cells and further applied this assay to characterize new heterologous promoters and differing attB chromosomal integration sites. These tools have, notably, been used to rapidly alter biosynthesis in S. venezuelae to improve titers of the D2 diesel alternative bisabolene.

  • Phelan, R. M.; Petkiewicz, S.; Barajas, J.; Rasor, B. J.; Blake-Hedges, J.; Katz, L.; Keasling, J.D. “Improved Biological Tools for the Rapid Engineering of Streptomyces venezuelaeIn preparation
  • Phelan, R. M.; Sekurova, O.; Zotchev, S.; Keasling, J. D. “Engineering Terpene Biosynthesis in Streptomyces venezuelae for the Production of the Advanced Biofuel Bisabolene.” ACS Synth. Biol. 2015, 4, 393-399

 

Complete List of Publications

11. Zargar, K.; Saville, R.; Phelan, R. M.; Tringe, S. G.; Petzold, C.; Keasling, J. D.; Beller, H. R. “In vitro characterization of phenylacetate decarboxylase, a novel enzyme catalyzing toluene biosynthesis in an anaerobic microbial community” Submitted

10. Barajas, J.*; Phelan, R. M.*; Schaub, A. J.; Kleiwer, J. T.; Luo, R.; Kelly, P. J.; Keasling, J. D.; Tsai, S.-C. “Comprehensive Structural and Biochemical Analysis of the Terminal Myxalamid Reductase Domain for the Engineered Production of Highly Reduced Alcohols” Chem. Biol. 2015, 22, 1018-1029
*Denotes equal contribution

9. Poust, S.; Phelan, R. M.; Deng, K.; Katz, L.; Petzold, C.; Keasling, J. D. “Divergent Mechanistic Routes for gem-Dimethyl Group Formation in Complex Polyketide Biosynthesis” Angew. Chem. Int. Ed. Engl. 2015, 54, 2370-2373

8. Phelan, R. M.; Sekurova, O.; Zotchev, S.; Keasling, J. D. “Engineering Terpene Biosynthesis in Streptomyces venezuelae for the Production of the Advanced Biofuel Bisabolene.” ACS Synth. Biol. 2015, 4, 393-399

7. Phelan, R. M.; Townsend, C. A. “Mechanistic Insights into the Bifunctional Non-Heme Iron Oxygenase Carbapenem Synthase by Active Site Saturation Mutagenesis” J. Am. Chem. Soc. 2013, 135, 7496-7502

6. Phelan, R. M.; DiPardo, B. J.; Townsend, C. A. “A High-Throughput Assay for the Engineered Production of β-Lactam Antibiotics” ACS Chem. Biol. 2012, 7, 835-840

5. Bodner, M. J.; Li, R.; Phelan, R. M.; Freeman, M. F.; Moshos, K. M.; Lloyd, E. P.; Townsend, C. A. “Definition of the Common and Divergent Steps in Carbapenem Biosynthesis” ChemBioChem, 2011, 12, 2159 – 2165

4. Bodner, M. J.; Phelan, R. M.; Freeman, M. F.; Li, R.; Townsend, C. A. “Non-Heme Iron Oxygenases Generate Natural Structural Diversity in Carbapenem Antibiotics” J. Am. Chem. Soc. 2010, 132, 12-13

3. Bodner, M. J.*; Phelan, R. M.*; Townsend, C. A. “A Catalytic Asymmetric Route to Carbapenems” Org. Lett. 2009, 11, 3606-3609
*Denotes equal contribution

2. Sohka, T.; Heins, R. A.; Phelan, R. M.; Greisler, J. M.; Townsend, C. A.; Ostermeier, M. “An Externally Tunable Bacterial Band-Pass Filter” Proc. Natl. Acad. Sci. U.S.A. 2009, 106, 10135-10140

1. Phelan, R. M.; Ostermeier, M.; Townsend, C. A. “Design and Synthesis of a β-Lactamase Activated 5- Fluorouracil Prodrug” Bioorg. Med. Chem. Lett. 2009, 19, 1261-1263

Patents

  1. Phelan, R. M., Keasling J. D. “Production of n-alcohols through the use of novel PKS-NRPS didomainhybrids” Submitted to LBNL Patent Office
  2. Townsend, C. A.; Bodner, M. J.; Phelan, R. M.; Freeman, M. F. “Method for the late introduction of the (8R)-hydroxyl group in carbapenem β-lactam antibiotic synthesis” Serial No. PCT/US2010/0600881

Awards

  1. N.S.F. Catalysis and Biocatalysis (PD 14-1401, issued to P.I. J.D.K.)
  2. Sarah and Adolph Roseman Achievement Award, Johns Hopkins University, 2011