主要研究方向为天然产物生物合成机制解析、关键生物合成酶挖掘与催化机制解析以及天然药物的新微生物细胞工厂构建与优化。成功阐明了麦角生物碱、莫匹罗星等微生物药物的复杂环系结构的生物合成机理，开展了真菌来源天然产物的特征环系结构的生物合成酶挖掘与新酶学机制解析，并通过人工生物合成途径改造设计，优化基因编辑工具以及开发新的底盘微生物细胞，研发出莫匹罗星、麦角生物碱、红曲红色素以及间甲酚的新发酵菌株，相关产品已经工业化并实现千吨级发酵。发表论文40 余篇，这些论文多次被权威综述杂志亮点报道、Faculty of 1000推荐、选为封面（底）故事、VIP论文以及JACS spotlights等。

 

代表论著：

 

图1：阐述临床首选局部抗感染药物莫匹罗星的生物合成途径（J. Am. Chem. Soc. 2014; Chem. Sci. 2014; Angewandte Chem. Int. Ed. 2014等）

 

图2：阐述真菌天然产物的生物合成途径（J. Am. Chem. Soc. 2016; J. Am. Chem. Soc. 2017; J. Am. Chem. Soc. 2018; Organ Lett 2022/2022等） 

 

图3. 解析了重要精神类疾病治疗药物麦角生物碱中央C环的合成机制，并构建了基于构巢曲霉的麦角生物碱药物的发酵新菌种（J. Am. Chem. Soc. , 2019; Metab. Eng., 2022等） 

 

图4. 构建适用于多核工业菌株的基因编辑系统，为生物制造类企业解决重大技术需求（ACS Syn Biol, 2020等）

2022年

23, Jun Zhang, Daohong Liao, Rongchang Chen, Fangfang Zhu, Yaqing Ma, Lei Gao, Ge Qu, Chengsen Cui,  Zhoutong Sun,* Xiaoguang Lei, * Shu-Shan Gao*, Tuning an Imine Reductase for the Asymmetric Synthesis of Azacycloalkylamines by Concise Structure-Guided Engineering. Angewandte Cheme International Edition, under revision.

22, Beyond the cyclopropyl ring formation: fungal Aj_EasH catalyzes asymmetric hydroxylation of ergot alkaloids. Chunyan An*, Fangfang Zhua, Yongpeng Yao, Kexin Zhang, Wei Wang, Jun Zhang, Guangzheng Wei, Yue Xia, Qiang Gao,*, Shu-Shan Gao,* Applied Microbiology and Biotechnology, 2022, in press.

21. Yongpeng Yao, Wei Wang, Wenyu Shi, Rui Yan, Jun Zhang, Guangzheng Wei, Ling Liu, Yongsheng Che, Chunyan An, Shu-Shan Gao*, Overproduction of medicinal ergot alkaloids based on a fungal platform, Metabolic Engineering, 2022, 69, 198-208 

 

2021年

19. Xian Shu, Guangzheng Wei, Yuben Qiao, Kexin Zhang, Jun Zhang, Guomin Ai, Man-cheng Tang, Yonghui Zhang, and Shu-Shan Gao*, TerC Is a Multifunctional and Promiscuous Flavoprotein Monooxygenase That Catalyzes Bimodal Oxidative Transformations. Org. Lett. 2021, 23, 22, 8947–8951 

18.  Guangzheng Wei,# Xian Shu,# Yongpeng Yao, Kexin Zhang, Jun Zhang, and Shu-Shan Gao*, Heterologous Production of Unnatural Flavipucine Family Products Provides Insights into Flavipucines Biosynthesis. Organic Letters, Org. Lett. 2021, 23, 20, 7708–7712 

17.  Wei Wang,# Chunyan An,# Yongpeng Yao, Xiangxi Meng, Shu-Shan Gao^* De novo biosynthesis and gram-level production of m-cresol in Aspergillus nidulans. Applied Microbiology and Biotechnology, 2021, 105, 6333–6343. 

 

2020年 

16. Weiwei Liu,# Chun-Yan An,# Xian Shu, Xiangxi Meng, Yongpeng Yao, Jun Zhang, Fusheng Chen, Hua Xiang, Shuyuan Yang, Xue Gao*, and Shu-Shan Gao.* A dual-plasmid CRISPR/Cas system for mycotoxin elimination in polykaryotic industrial fungi, ACS Synthetic Biology, 2020, 9, 8, 2087–2095. 

 

2019年 

15. Yongpeng Yao,# Chunyan An,# Declan Evans, Weiwei Liu, Wei Wang, Guangzheng Wei, Ning Ding, K. N. Houk,* Shu-Shan Gao.* A catalase involved in the oxidative cyclization of the tetracyclic ergoline of fungal ergot alkaloids. Journal of the American Chemical Society 2019, 141, 44, 17517-17521. 

14. Mengbin Chen, Qikun Liu, Shu-Shan Gao, Abbegayle E. Young, Steven E. Jacobsen, and Yi Tang. Genome mining and biosynthesis of a polyketide from a biofertilizer fungus that can facilitate reductive iron assimilation in plant. PNAS, 2019, 116, 12, 5499-5504.

13. Tingting Hao, Zhoujie Xie, Min Wang, Liwei Liu, Yuwei Zhang, Weicang Wang, Zhao Zhang, Xuejin Zhao, Pengwei Li, Zhengyan Guo, Shushan Gao, Chunbo Lou, Guodong Zhang, Justin Merritt, Geoff P. Horsman & Yihua Chen*, An anaerobic bacterium host system for heterologous expression of natural product biosynthetic gene clusters, Nature Communications 2019, 10, 1, 3665. 

 

2018年 

12. 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, 140, 2067-2071.

11. 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 2018, 140, 6991-6997.

10. Shu-Shan Gao,# Ronghai Cheng,# Nathchar Naowarojna,# Xueting Liu,* and Pinghua Liu,* Recent examples of α-ketoglutarate dependent mononuclear non-haem iron enzymes in natural product biosyntheses. Natural Product Reports 2018, 35, 8, 792-837.

 

2017年 

9. 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, 3930？3934 (Back Cover and VIP Paper).

8. 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.

7. 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, 5317-5320.

6. 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年 

5. 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, 2066-2074.

4. Shu-Shan Gao, Abing Duan, Wei Xu, Peiyuan Yu, Leibniz Hang, K. N. Houk, Yi Tang.* 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, 15837-15840.

 

2014年 

2. 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, 5501-5507. (Highlighted in Natural Products Reports).

1. 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, 397-402. (Highlighted in Natural Products Reports). 

 

2014年前发表论文 

1.   Chun-Shun Li, Xiao-Ming Li, Shu-Shan Gao, Yan-Hua Lu, Bin-Gui Wang.* Cytotoxic Anthranilic Acid Derivatives from Deep Sea Sediment-Derived Fungus Penicillium paneum SD-44, Marine drugs, 2013, 11, 3068-3076. 

2.   Chun-Yan An, Xiao-Ming Li, Chun-Shun Li, Shu-Shan Gao, Zhuo Shang, Bin-Gui Wang.* Triazoles and Other N-Containing Metabolites from the Marine-Derived Endophytic Fungus Penicillium chrysogenum EN-118, Helvetica Chimica Acta, 2013, 96, 682-687. 

3.   Hao-Fen Sun, Xiao-Ming Li, Ling-Hong Meng, Chuan-Ming Cui, Shu-Shan Gao, Chun-Shun Li, Bin-Gui Wang.* Two New Secoanthraquinone Derivatives from the Marine-Derived Endophytic Fungus Aspergillus wentii EN-48,  Helvetica Chimica Acta, 2013, 96, 458-462. 

4.   Hong Sun, Shu-Shan Gao, Xiaoming Li, Chunshun Li, Bingui Wang.* Chemical constituents of marine mangrove-derived endophytic fungus Alternaria tenuissima EN-192, Chinese Journal of Oceanology and Limnology, 2013, 31, 464-470. 

5.   Hong Sun, Shu-Shan Gao, Xiao-Ming Li, Chun-Shun Li, Bin-Gui Wang.* Chemical constituents of marine mangrove-derived endophytic fungus Alternaria tenuissima EN-192. Chinese Journal of Oceanology and Limnology 2013, 31, 464-470. 

6.   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, 256-261. 

7.   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, 59-70. 

8.   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, 2894-2897. 

9.   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, 1748-1753. 

10.  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, 358-360. 

11. 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, 1477-1480. 

12. 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, 1331-1334. 

13.  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, 148-152. 

14. 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, 1787-1791. 

15.  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. 

16.  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, 1366-1370. 

17.  Zhuo Shang, Xiaoming Li, Li Meng, Chunshun Li, Shu-shan Gao, Caiguo Huang, Bingui Wang.* Chemical profile of the secondary metabolites produced by a deep-sea sediment-derived fungus Penicillium commune SD-118, Chinese Journal of Oceanology and Limnology, 2012, 30, 305-314. 

 

申请或授权专利

1. 王斌贵，高书山，李晓明，一种单萜衍生物及其制备和应用, 申请号：201010141405.9；专利号：ZL201010141405.9

2. 王斌贵，高书山，李晓明，一种多羟基甾醇衍生物及其制备和应用, 申请号：201010209248.0；专利号：ZL201010209248.0

3. 王斌贵，高书山，李晓明，一种Azaphilone类衍生物及其制备和应用，申请号：201010515606.0；专利号： ZL201010515606.0

4. 王斌贵，高书山，李晓明，一种四环二萜类衍生物的应用，申请号：201010620672.4；专利号： ZL201010620672.4

5. 王斌贵；孙好芬；李晓明；李春顺；崔传明；高书山，一种双内酯类衍生物及其制备方法和应用，申请号：201010557924.3；专利号： ZL201010557924.3

6. 王斌贵，孙好芬，黄才国，孟莉，李晓明，李春顺，崔传明，高书山,一种四降二萜双内酯类衍生物在制备抗肿瘤药物中的应用，申请号：201010557924.3；专利号： ZL201110022009.9