1. 논문관련 분야의 소개, 동향, 전망을 설명, 연구과정에서 생긴 에피소드

본 논문 “The chloroalkaloid (−)-acutumine is biosynthesized via a Fe(II)- and 2-oxoglutarate-dependent halogenase in Menispermaceae plants”, we present the discovery of the first plant halogenase (dechloroacutumine halogenase; DAH).

Halogenated natural compounds like vancomycin, chloramphenicol (antibiotics), etc. are of huge medicinal interest, and it turns out, they are relatively rare in plants.

Plants, as sessile organisms, are excellent chemists and can catalyzing interesting, highly efficient chemical reactions. In this case, Moonseed vines can perform site-selective halogenation in the biosynthesis of an unusual tetracyclic chloroalkaloid, acutumine, which is a potential anti-leukemia drug. The discovery of DAH not only elucidates the terminal chlorination step of acutumine biosynthesis but also provides opportunities to think about how we can engineer plant systems to derivatize already-potent plant natural compounds for producing drugs with new bioactivities.

For more information and news press by Whitehead Institute:
http://wi.mit.edu/news/archive/2020/harnessing-moonseed-plant-s-chemical-know-how.

연구과정에서 생긴 에피소드: 3 months after joining Jing-Ke Weng’s lab at the Whitehead Institute, one of the postdocs, Andrew Mitchell, in our lab approached me with a potential project I could pursue-he had insights on Fe(II)-2OG-dependent halogenases, and I still remember sitting down with him and discussing how this could lead to an impactful discovery. I am extremely thankful for his mentorship!

2. 연구를 진행했던 소속기관 또는 연구소에 대해 소개 부탁 드립니다.

저는 Massachusetts Institute of Technology/Whitehead Institute, Jing-Ke Weng 교수님 연구실에서 Biological Engineering 박사 과정 공부를 하고있습니다. The Weng Lab investigates the origin and evolution of plant specialized metabolism at enzyme, pathway, and systems levels, and also focuses on how plants biosynthesize small molecules to interact with their surrounding biotic and abiotic stimulus.
For more information on our lab’s research : http://wenglab.wi.mit.edu/

Whitehead Institute (WI) is a wonderful biomedical research institute located in the heart of Kendall Square in Cambridge, MA, USA. I am extremely honored and privileged to be training at a fantastic institute rich in resources and filled with collaborations across all disciplines. I am especially thankful for all the research cores (metabolomics, genomics, functional genomics, proteomics, media, imaging, etc.), along with the collaborative spirit of all the faculty at the WI.
For more information on WI: http://wi.mit.edu

3. 연구활동 하시면서 평소 느끼신 점 또는 자부심, 보람

The best part about scientific research is the freedom and independence to explore my curiosity in any areas that I am interested in. In reality, however, research can be a challenging and lonely process- a colleague of mine once told me “it takes 20% of the effort to complete the first 80% of the work, then it takes 80% effort to complete the final 20%”. The process of writing my first manuscript was exciting, but also mentally strenuous! During these times, it was beneficial to have great outlets to destress and take my mind off of my work. Ultimately though, the driving motivation to complete my work comes from my passion to make novel discoveries and share them with those in the scientific communities. I find that very fulfilling!

4. 이 분야로 진학하려는 후배들 또는 유학준비생들에게 도움이 되는 말씀을 해 주신다면?

An advice that I have for any undergraduate students or prospective graduate students in the field of natural product biosynthesis/synthetic biology/chemical biology is to be proactive and get yourself involved in cutting-edge research! Apply to research programs and go outside your comfort zone to reach out to professors and be trained under passionate mentors. I truly believe that the future of chemical synthesis relies on the growing toolbox of enzyme biocatalysts, along with new technologies being developed in the metabolic engineering field. Developing your passion and interests is the most important thing before choosing to enter into any given field-can do this by reading review papers on the topics and discussing with researchers in the field!

5. 연구활동과 관련된 앞으로의 계획이 있으시다면?

Moving forward, I will continue to explore the diversity of plant natural products and characterize their biosynthetic pathways. There is also a huge potential in evolving DAH to catalyze C-H functionalization on related alkaloids.

6. 다른 하시고 싶은 이야기들....

First of all, I would like to thank all the co-authors on this study and my PI, Jing-Ke Weng for their tremendous support and feedback on this work. I also would like to thank my former my undergraduate mentors Irene Chen (UCSB, now UCLA) and Christina Smolke (Stanford). I am always thankful for the lasting influence that all my mentors had in my academic career. Lastly, I would like to thank my family and friends for their support as well.