Athavale, Soumitra

Short Biography

Soumitra was born and raised in Pune, India. Following BS-MS studies in Chemistry and Biology at IISER Pune, he travelled to the US for doctoral research at the University of Illinois, Urbana-Champaign under the supervision of Prof. Scott E. Denmark. Soumitra’s PhD was focused on elucidating the mechanism of the Soai reaction. This extraordinary transformation displays the unique phenomenon of amplifying asymmetric autocatalysis, can generate enantioenriched products starting from achiral reactants by spontaneous symmetry breaking, and has received widespread attention from diverse chemical fields. Its mechanism had remained elusive for more than two decades. Soumitra’s investigations have produced the first comprehensive mechanistic picture of this iconic reaction and provide a foundation for further explorations in the field of asymmetric autocatalysis and the evolution of homochirality.

Soumitra joined Professor Frances H. Arnold’s group at Caltech as a postdoctoral scholar, expanding his expertise into protein engineering and directed evolution. He was involved in the development of nitrene transferase enzymes, breaking new ground in the nitrogen functionalization of C–H bonds. The enzymes Soumitra has worked on have contributed to the asymmetric C–H amidation of benzylic positions, and the site and enantioselective derivatization of unactivated and unbiased C–H bonds, a reaction unprecedented in both biology and synthetic chemistry. They can be considered as the nitrogen counterparts of the venerable P450 heme-monooxygenases. The research opens new opportunities for the biocatalytic manufacturing of nitrogen compounds, will assist fundamental enzymological studies of nitrene transfer reactions, and may inspire the design new pathways for nitrogen metabolism.

Soumitra joined the UCLA department of Chemistry and Biochemistry as an Assistant Professor in July 2023.

Research Interests

The Athavale group has a broad interest in synthetic organic chemistry, (bio)molecular evolution and chemical biology, with research encompassing four main themes:

  1. Synthetic chemistry and biocatalysis. The group explores new methodologies for challenging bond disconnections using main group chemistry, photoredox catalysis and biocatalysis. A special emphasis is on utilizing the tools of directed evolution for the development of novel enzymology to solve classical challenges in asymmetric synthesis.
  2. The ‘organic chemistry of evolution’: exploring molecular evolution beyond biology. This program aims to pursue the assembly of artificial, synthetic (proto)evolutionary systems to reveal the essential design principles that enable evolutionary behavior.
  3. Fundamental relationships in enzyme structure and function. This research addresses questions like the minimum sequence length for functional enzymes and the evolution of early biochemical catalysts, utilizing innovative directed evolution approaches to tackle classical problems in protein structure and peptide evolution.
  4. Engineered Enzymes as Next-Generation Synergetic Co-Therapeutics. The group focuses on developing engineered enzymes as cutting-edge therapeutics, targeting metabolic enzymes that enhance drug action, improve efficacy, and promote safety. This program fuses state-of-the-art protein engineering with practical medical applications.

Honors & Awards

  • Finalist, Merck Research Award for Underrepresented Chemists of Color, 2021.
  • ACS Green Chemistry Institute (ACS GCI) Pharmaceutical Roundtable Student Travel Grant, 2021.
  • Co-winner, 2nd Merck Compound Challenge 2020 – a global retrosynthesis competition that saw participation from 132 teams.
    Participated and won as a single-member team. The other winner was a ten-member group from MPI, Mulheim, Germany.
    News highlights by Merck, Merck India, Chemistry UIUC, Bio-Patrika.  
  • ACS Green Chemistry Institute, Pharmaceutical Roundtable (ACS-GCIPR) Research Grant, 2020.
  • Coleman Fellowship 2017-2018, Chemistry Department, UIUC. 
  • Departmental Fellowship 2015-2016, Chemistry Department, UIUC.
  • DAAD-WISE 2012 Fellow for summer internship at the University of Gottingen, Germany. 
  • CSIR-JRF All India Rank 31 (Dec 2012 NET). 
  • INSPIRE Fellowship from Department of Science and Technology (DST), India during study at IISER Pune (2008-2013). 
  • Gold Medal at the Indian National Chemistry Olympiad Training Camp for IChO 2008 at HBCSE, TIFR. 

Representative Publications

Below is a list of selected publications:

12. Book chapter: Demystifying the Soai Reaction
Athavale, S. V.
; Denmark, S. E.
in Asymmetric Autocatalysis: The Soai Reaction Soai, K.; Kawasaki, T.; Matsumoto, A.; Eds.,
The Royal Society of Chemistry 2023, ISBN:978-1-83916-261-9.

11. Enzymatic Nitrogen Insertion into Unactivated C–H bonds
Athavale, S. V.* ( * co-corresponding author); Gao, S.; Das, A.; Mallojjala, S.; Alfonzo, E.; Long, Y.; Hirschi, J. S.; Arnold, F. H.
J. Am. Chem. Soc. 2022, 144 (41), 19097-19105.
Highlighted by Derek Lowe – ‘Zapping in Amine Groups’- on his blog ‘In the Pipeline’ hosted by Science magazine.
Highlighted by Benjamin List and Marian Guillén in Synfacts 2023; 19(01): 0081 ‘Enzymatic Amination and Amidation of Unactivated Csp3–H Sites’

10. An Enzymatic Platform for Primary Amination of 1-Aryl-2-alkyl Alkynes
Liu, Z.; Qin, Z.; Zhu, L.; Athavale, S. V.; Sengupta, A.; Jia, Z.; Garcia-Borras, M.; Houk, K. N.; Arnold, F. H.
J. Am. Chem. Soc. 2022, 144 (1), 80-85.

9. Book chapter: Engineering Enzymes for New-to-Nature Carbene Chemistry 
Athavale, S. V.; Chen, K.; Arnold, F. H.
in Transition Metal-Catalyzed Carbene Transformations. Wang, J; Che, C-M.; Doyle, M. P., Eds.,
Wiley-VCH 2022, pp 95-138.

8. Perspective: Combining Chemistry and Protein Engineering for New-to-nature Biocatalysis
Miller, D.; Athavale, S. V.; Arnold, F. H.
Nat. Synth.
 2022, 1, 18-23

7. Biocatalytic, Intermolecular C-H Bond Functionalization for the Synthesis of Enantioenriched Amides
Athavale, S. V.; Gao, S.; Liu, Z.; Mallojjala, S.; Hirschi, J. S.; Arnold, F. H.
Angew. Chem. Int. Ed. 2021, 60 (47), 24864-24869.

6. Essay: The Katalytic Speedometer
Athavale, S. V.
Nat. Phys. 2020, 16, 704.

5. Structural Contributions to Autocatalysis and Asymmetric Amplification in the Soai Reaction
Athavale, S. V.; Simon, A.; Houk, K. N.; Denmark, S. E.
J. Am. Chem. Soc. 2020, 142 (43), 18387-18406.

4. Demystifying the Asymmetry-Amplifying, Autocatalytic Behaviour of the Soai Reaction through Structural, Mechanistic and Computational Studies
Athavale, S. V.; Simon, A.; Houk, K. N.; Denmark S. E.
Nat. Chem. 2020, 12 (4), 412-423.
Highlighted by Chemistry World (‘Mirror-symmetry breaking reaction’s mechanism solved after 25 years’), Science, Chemistry UIUC, Chemistry UCLA, Bio-Patrika.

3. Review: Quantitative Structure–Selectivity Relationships in Enantioselective Catalysis: Past, Present, and Future
Zahrt, A. F.; Athavale, S. V.; Denmark, S. E.
Chem. Rev. 2020, 120 (3), 1620-1689.

2. Unusual Kinetic Profiles for Lewis Base-Catalyzed Sulfenocyclization of Ortho-Geranylphenols in Hexafluoroisopropyl Alcohol
Robb, K. A.; Athavale, S. V.; Denmark, S. E.
Synlett 201930 (14), 1656–1661.

1. A Versatile Toolbox for Posttranscriptional Chemical Labeling and Imaging of RNA
Sawant, A. A.; Tanpure, A. A.; Mukherjee, P. P.; Athavale, S.; Kelkar, A.; Galande, S.; Srivatsan, S. G.
Nucleic Acids Res. 2016, 44 (2), e16–e16.