Microbial Natural Product Discovery and Biosynthesis Group

 

Principle investigator: Dr. Shu-Shan Gao

Tel: 010-64806089

Email: gaoss@im.ac.cn

Research area

Genome mining; Enzymology; Synthetic biology; P450 Engineering

 

Research interest

 

1) New drug lead discovery: Microbials are the most important source for the drug leads. In our lab, we used a combination of modern research strategies to search or engineering drug leads from microbials. We have developed a platform combining genome mining and synthetic biology to uncover the fast potential of fungi isolated from different environments. We also applied the protein engineering for the structural diversification or semisynthesis of the well-known drugs on-market.

 

2) Natural product biosynthesis: Microbials are the best chemist in Nature. They can generate tremendous chemical diversity from simple building blocks, by assembling diverse enzymes into biosynthetic pathways towards the synthesis of the complex natural products. Our goal is to understand the biochemical and structural basis of different enzymes encoded in these pathways. By accumulating biosynthetic knowledge and enzymatic tools, we aim towards the engineered biosynthesis of unnatural natural products through combinatorial biosynthesis.

 

3) Enzyme engineering for new chemistry: Enzymes are biocatalysts used by Nature to apply the diverse chemical reactions, which are essential for maintaining life activities and primary/secondary metabolism. We aim to expand their chemistry by batch screening and direct evolution, which would bring us with potential biocatalysts for industrial purpose.


Group members

 


Principle investigator

Shu-Shan Gao, Ph.D., Principal Investigator, Associate Professor, gaoss@im.ac.cn

 

Education

2006-2011, Ph.D Institute of Oceanology, Chinese Academy of Sciences

 

Professional Experience

2011-2014, Research Assistant, School of Chemistry, University of Bristol, United Kingdom

2014-2017, Postdoctoral Researcher, University of California, Los Angeles, United States

2017-2018, Professor, Hunan University, China

2018-, Principle investigator, Associate Professor, Institute of Microbiology, Chinese Academy of Sciences



Permanent stuff

Meng Xiangxi


Natural product biosynthesis

 

Yao Yongpeng

Protein engineering


 


Graduate students

Wang Wei

Protein Engineering

 



Visiting scholar

Wei Guangzheng

Natural product biosynthesis


Jiang nan

Genome mining for new terpene scaffolds


 

Recent Publications

 

2018

 

1. Li Li, Man-Cheng Tang, Shoubin Tang, Shu-Shan Gao, sameh.S.M soliman, Leibniz Hang, Wei Xu, Tao Ye, Kenji Watanabe, and Yi Tang Genome Mining and Assembly-Line Biosynthesis of the UCS1025A Pyrrolizidinone Family of Fungal Alkaloids. Journal of the American Chemical Society, 2018, 10.1021/jacs.8b00056

 

2. Shu-Shan Gao#, Tao Zhang#, Marc Garcia-Borràs, Yiu-Sun Hung§, John M. Billingsley, K. N. Houk*, Youcai Hu*, and Yi Tang*, Biosynthesis of Heptacyclic Duclauxins Requires Extensive Redox Modifications of the Phenalenone Aromatic Polyketide, Journal of the American Chemical Society (In Press).

 

3. Shu-Shan Gao,# Ronghai Cheng,# Nathchar Naowarojna,# Xueting Liu,* and Pinghua Liub,* Recent Examples of α-Ketoglutarate Dependent Mononuclear Non-Haem Iron Enzymes in Natural Product Biosyntheses. Natural Product Reports (In Press)

 

 

2017

 

1. Shu-shan Gao,# Luoyi Wang,# Zhongshu Song, Joanne Hothersall, Russell J. Cox, Matthew P. Crump, Paul Race, Christopher M. Thomas, Christine L. Willis* and Thomas J. Simpson* Selected Mutations Reveal New Intermediates in the Biosynthesis of the Thiomarinols and Mupirocin Antibiotics, Angewandte Chemie International Edition, 2017, 56, 39303934 (Back Cover and VIP Paper).

 

2. Shu-Shan Gao, Marc Garcia-Borràs, Joyann S. Barber, Yang Hai, Abing Duan, Neil K. Garg, K. N. Houk, Yi Tang§, Enzyme-Catalyzed Intramolecular Enantioselective Hydroalkoxylation. Journal of the American Chemical Society, 2017, 139, 3639–3642.

 

3. Michio Sato, Jacob E Dander, Chizuru Sato, Yiu-sun Hung, Shu-Shan Gao, Man-Cheng Tang, Leibniz Hang, Jaclyn M Winter, Neil K Garg, Kenji Watanabe, Yi Tang. Collaborative Biosynthesis of Maleimide-and Succinimide-Containing Natural Products by Fungal Polyketide Megasynthases. Journal of the American Chemical Society, 2017, 139, 53175320.

 

4. Nicholas Liu, Yiu-Sun Hung, Shu-Shan Gao, Leibniz Hang, Yi Zou, Yit-Heng Chooi, and Yi Tang. Identification and Heterologous Production of a Benzoyl-Primed Tricarboxylic Acid Polyketide Intermediate from the Zaragozic Acid A Biosynthetic Pathway. Organic Letters, 2017, 19, 3560–3563.

 

2016

 

1. Shu-Shan Gao, Xiao-Ming Li, Katherine Williams, Peter Proksch, Nai-Yun Ji, and Bin-Gui Wang. Rhizovarins A–F, Indole-Diterpenes from the Mangrove-Derived Endophytic Fungus Mucor irregularis QEN-189. Journal of Natural Products, 2016, 79, 20662074.

 

2. Shu-Shan Gao, Abing Duan, Wei Xu, Peiyuan Yu, Leibniz Hang, K. N. Houk,Phenalenone Polyketide Cyclization Catalyzed by Fungal Polyketide Synthase and Flavin-Dependent Monooxygenase. Journal of the American Chemical Society 2016, 138, 4249–4259. (JACS Spotlight article, Highlighted in Natural Products Reports)

 

3. Li Li, Peiyuan Yu, Man-Cheng Tang, Yi Zou, Shu-Shan Gao, Yiu-Sun Hung, Muxun Zhao, Kenji Watanabe, Kendall N Houk, Yi Tang. Biochemical Characterization of a Eukaryotic Decalin-Forming Diels–Alderase. Journal of the American Chemical Society, 2016, 138, 1583715840.

 

2014

 

1. Shu-Shan Gao,# Joanne Hothersall,# Ji’en Wu, Annabel C. Murphy, Zhongshu Song, Elton R. Stephens, Christopher M. Thomas, Russell J. Cox, Thomas J. Simpson, and Christine L. Willis. The Biosynthesis of Mupirocin by Pseudomonas fluorescens NCIMB 10586 Involves Parallel Pathways, Journal of the American Chemical Society, 2014, 136, 55015507. (Highlighted in Natural Products Reports)

 

2. Annabel C. Murphy#, Shu-Shan Gao#, Li-Chen Han, Daisuke Fukuda, Zhongshu Song, Joanne Hothersall, Simon Carobene, Russell J. Cox, John Crosby, Christine L. Willis, Christopher M. Thomas and Thomas J. Simpson, Biosynthesis of Thiomarinol A and Related Metabolites of Pseudoalteromonas SANK73390. Chemical science, 2014, 5, 397402. (Highlighted in Natural Products Reports)

 

Before 2014

 

1. Shu-Shan Gao, Xiao-Ming Li, Yi Zhang, Chun-Shun Li, Chuan-Ming Cui, and Bin-Gui Wang. Comazaphilones A-F, azaphilone derivatives from the marine sediment-derived fungusPenicillium commune QSD-17. Journal of Natural Products, 2011 ,74, 256261.

 

2. Shu-Shan Gao, Xiao-Ming Li, Feng-Yu Du, Chun-Shun Li, Peter Proksch and Bin-Gui Wang. Secondary metabolites from a marine-derived endophytic fungus Penicillium chrysogenum QEN-24S. Marine Drugs, 2011, 9, 5970.

 

3. Shu-Shan Gao, Xiao-Ming Li, Chun-Shun Li, Peter Proksch, and Bin-Gui Wang. Penicisteroids A and B, antifungal and cytotoxic polyoxygenated steroids from the marine alga-derived endophytic fungus Penicillium chrysogenum QEN-24S. Bioorganic & Medicinal Chemistry Letters, 2011, 27, 28942897.

 

4. Shu-Shan Gao, Xiao-Ming Li, Yi Zhang, Chun-Shun Li and Bin-Gui Wang. Conidiogenones H and I, two new diterpenes of cyclopiane class from a marine-derived endophytic fungus Penicillium chrysogenum QEN-24S. Chemistry & Biodiversity, 2011, 8, 17481753.

 

5. Shu-Shan Gao, Zhuo Shang, Xiao-Ming Li, Chun-Shun Li, Chuan-Ming Cui and Bin-Gui Wang, Secondary Metabolites Produced by Solid Fermentation of the Marine-Derived Fungus Penicillium commune QSD-17. Bioscience, Biotechnology, and Biochemistry. 2012, 76, 358360.

 

6. Shu-Shan Gao, Xiao-Ming Li and Bin-Gui Wang. Perylene derivatives produced by Alternaria alternata, an endophytic fungus isolated from Laurencia Species. Natural Product Communications, 2009, 4, 14771480.

 

7. Cytotoxic Anthranilic Acid Derivatives from Deep Sea Sediment-Derived Fungus Penicillium paneum SD-44. CS Li, XM Li, SS Gao, YH Lu, BG Wang, Marine drugs, 2013, 11, 30683076.

 

8. Chun-Shun Li, Chun-Yan An, Xiao-Ming Li, Shu-Shan Gao, Chuan-Ming Cui, Hao-Fen Sun and Bin-Gui Wang, Triazole and dihydroimidazole alkaloids from the marine sediment-derived fungus Penicillium paneum SD-44. Journal of Natural Products, 2011, 74, 13311334.

 

9. Hao-Fen Sun, Xiao-Ming Li, Li Meng, Chuan-Ming Cui, Shu-Shan Gao, Chun-Shun Li, Cai-Guo Huang and Bin-Gui Wang, Asperolides A-C, tetranorlabdane diterpenoids from the marine alga-derived endophytic fungus Aspergillus wentii EN-48. Journal of Natural Products, 2012, 75, 148152.

 

10. Dong Liu, Xiao-Ming Li, Li Meng, Chun-Shun Li, Shu-Shan Gao, Zhuo Shang, Peter Proksch, Cai-Guo Huang and Bin-Gui Wang, Nigerapyrones A-H, α-pyrone derivatives from the marine mangrove-derived endophytic fungus Aspergillus niger MA-132. Journal of Natural Products, 2011, 74, 17871791.

 

11. Hui-Jiao Yan, Shu-Shan Gao, Chun-Shun Li, Xiao-Ming Li and Bin-Gui Wang. Chemical constituents of a marine-derived endophytic fungus Penicillium commune G2M, Molecules 2010, 15, 3270-3275.

 

12. Chuan-Ming Cui, Xiao-Ming Li, Chun-Shun Li, Hao-Fen Sun, Shu-Shan Gao, Bin-Gui Wang, Benzodiazepine alkaloids from marine-derived endophytic fungus Aspergillus ochraceus, Helvetica Chimica Acta, 2009, 92, 13661370.

 

13. Triazoles and Other N-Containing Metabolites from the Marine-Derived Endophytic Fungus Penicillium chrysogenum EN-118. CY An, XM Li, CS Li, SS Gao, Z Shang, BG Wang, Helvetica Chimica Acta, 2013, 96, 682687.

 

14. Two New Secoanthraquinone Derivatives from the Marine-Derived Endophytic Fungus Aspergillus wentii EN-48. HF Sun, XM Li, LH Meng, CM Cui, SS Gao, CS Li, BG Wang,  Helvetica Chimica Acta, 2013, 96, 458462.

 

15. Chemical constituents of marine mangrove-derived endophytic fungus Alternaria tenuissima EN-192. H Sun, S Gao, X Li, C Li, B Wang, Chinese Journal of Oceanology and Limnology, 2013, 31, 464470.

 

16.   Chemical profile of the secondary metabolites produced by a deep-sea sediment-derived fungus Penicillium commune SD-118, Z Shang, X Li, L Meng, C Li, SS Gao, C Huang, B Wang, Chinese Journal of Oceanology and Limnology, 2012, 30, 305314.