Chunshuai Huang
CONTACT
huangchunshuai@simm.ac.cn
+86-0535-6821723
201203
Shandong Laboratory of Yantai Drug Discovery, Bohai Rim Advanced Research Institute for Drug Discovery, Yantai, Shandong 264117, China
Biography
Chunshuai Huang obtained his PhD in Marine Biology from the University of Chinese Academy of Sciences under the supervision of Prof. Changsheng Zhang. Following his postdoctoral training in Prof. Huimin Zhao’s lab at University of Illinois at Urbana-Champaign, he joined the Shanghai Institute of Materia Medica, Chinese Academy of Sciences as a professor. His research focuses on the development and application of synthetic biology tools to discover novel natural products, elucidation of their chemical structures, and characterization of their biosynthetic mechanisms.
Education Experience：
Ph.D. in Marine Biology Sep.2014 – Jun.2018 South China Sea Institute of Oceanology, CAS, Guangzhou, China
M.P. in Pharmaceutical Chemistry Sep.2011 – Jun.2014 Kunming Institute of Botany, CAS, Kunming, China
B.A. in Agronomy Sep.2007 – Jun.2011 School of Resources, Southwest Forestry University, Kunming, China
Work Experience：
Postdoctor in Synthetic Biology Oct.2018 – Apr.2023
Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL, USA
Professor in Natural Product Chemistry and Synthetic Biology Apr.2023 – up to now
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
Research Directions
Based on the most cutting-edge technologies in direct cloning and directed evolution that our group has mastered, we are going to carry out the following directions:
1) Discovery of novel bioactive natural products
Utilize the highly robust strategy CAPTURE to quickly clone the biosynthetic gene clusters of interest from microorganisms to discover novel bioactive natural products.
2) Biosynthesis and enzymology
Unveil the unique biosynthesis mechanisms and elucidate the mechanistic enzymology.
3) Enzyme biocatalysis
Expand the application of enzymatic catalysis in drug development.
Grants & Research Projects
National Natural Science Foundation of China
Shanghai Pujiang Program
Achievements
Natural products are the important resources for lead compound discovery and pharmaceutical development. Our group focuses on the two hot areas of natural product chemistry and synthetic biology and has made a series of original achievements.
Firstly, two robust direct cloning methods, CAPTURE and FAST-NPs, have been developed. Heterologous expression of part of those cloned BGCs has led to the discovery of two classes of unprecedented carbon skeletons: bipentaromycins and allenomycins.
Secondly, a large number of novel di-/trimeric aromatic polyketides with varied C−C and C−N coupling patterns have been isolated and characterized from heterologous host expressing the fluostatin (FST) gene cluster. These dimers have been demonstrated to be derived from non-enzymatic deacylation of acyl FSTs. The non-enzymatic deacylation proceeds via a transient quinone methide like intermediate which facilitates the subsequent C–C/C−N coupled dimerization. This mechanism is revealed for the first time and has been applied to the assembly of C–C and C–N coupled aromatic polyketide dimers. Notably, the functions and mechanisms of several enzymes involved in the biosynthesis of FSTs have been unveiled.
Thirdly, by integrating heterologous expression, isotope labeling, gene knockout and complementation, and computational modeling, the applicant determined the biosynthetic origin of the skeleton of bipentaromycins, identified the enzymes involved in stereo-/regioselective hydrogenation and methylation, and provided new mechanistic insights into the dimerization.
Our group have published 24 papers in famous journals, such as Nat. Chem., Nat. Commun., JACS Au, PNAS, Angew. Chem. Int. Ed., Org. Lett..
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Social Titles
Member of Marine Drugs Professional Committee, Chinese
Pharmaceutical Association
Member of Marine Drugs Professional Committee,
Shanghai Pharmaceutical Association
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Awards & Honors
President’s special award of University of Chinese Academy of Sciences, Beijing, China
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Pubilcations
Full Publication List
Selected Publications
1. C. Huang#, et al. Molecular basis of dimer formation during the biosynthesis of benzofluorene-containing atypical angucyclines. Nature Communications, 2018, 9(1): 2088.
2. H. Ren#, C. Huang#, et al. Non-modular fatty acid synthases yield distinct N-terminal acylation in ribosomal peptides. Nature Chemistry, 2024, 16(8): 1320.
3. B. Enghiad#, C. Huang#, et al. Cas12a assisted precise targeted cloning using in vivo Cre-lox recombination. Nature Communications, 2021, 12(1): 1171.
4. C. Huang, et al. Investigation of the biosynthetic mechanism of bipentaromycin featuring an unprecedented cyclic head-to-tail dimeric scaffold. JACS Au, 2023, 3(1), 195.
5. C. Huang, et al. Discovery of an unexpected 1,4-oxazepine-linked seco-fluostatin heterodimer by inactivation of the oxidoreductase-encoding gene flsP. Journal of Natural Products, 2021, 84(8): 2336.
6. C. Yang#, C. Huang#, et al*. Inactivation of flavoenzyme-encoding gene flsO1 in fluostatin biosynthesis leads to diversified angucyclinone derivatives. The Journal of Organic Chemistry, 2021, 86(16): 11019.
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