刘成伟教授，博士生导师

联系方式：

E-mail:liuchw@nefu.edu.cn

电话：18246118378

地址：黑龙江省哈尔滨市香坊区和兴路26号

beat365官方网站(新逸夫教学楼) 617房间

教育和训练经历:

2014/04 ~ 2015/10 日本北海道大学大学院理学研究院化学部门 博士后

2011/04 ~ 2014/03 日本北海道大学,综合化学院 博士

2009/04 ~ 2011/03 日本秋田县立大学,生物资源研究科硕士

2008/03 ~ 2009/03 日本秋田县立大学,生物资源研究科研究生

工作经历:

2019/11 ~至今 beat365官方网站 教授

2015/11 ~ 2019/09北海道大学大学院理学研究院化学部门 助理教授

2004/08 ~ 2008/02 东阳光集团制药部门 研究员

专业特长:

合成生物学，天然产物化学，次级代谢产物生物合成途径解析…。

研究经验和研究领域:

植物，微生物生产的天然产物是重要的医药资源，为人类的健康做出了巨大的贡献，本课题组主要研究内容是天然产物的生物合成途径解析。通过基因组编辑技术（CRISPR/Cas9）和米曲霉异源表达的方法，对具有生理活性物质的生物合成途径进行分析，解明酶促反应机理。探索和激活具有潜在功能的基因，挖掘新的天然产物。并且通过基因编辑以及异源表达等方法，高效生产具有应用价值的化合物。研究内容主要归纳为以下几个方向：

研究方向一：大型真菌（蘑菇）次级代谢产物的生物合成途径解析：

许多蘑菇菌类具有广泛的医用价值，比如自古以来就被用于中药药材的灵芝，桑黄等，具有解毒，活血，增强免疫力，抗衰老等功效。但具有这些功效的天然产物还没有完全被确定，这是由于蘑菇对栽培条件要求苛刻，基因操作困难，导致蘑菇菌类生产的天然产物的生物合成研究相对匮乏。我们最近应该米曲霉表达系统，成功解明了猴头菇生产的猴头菌素（erinacine）的生物合成途径。在此基础上将继续对有应用价值的大型真菌生产的天然产物生物合成途径进行研究。

研究方向二：激活具有潜在功能基因，挖掘新化合物：

近年来，随着基因组技术的发展，必要的基因组信息可以在短时间内获得。通过这些信息可以清楚地看到，存在于微生物中的许多次级代谢产物生物合成基因的转录活性受到了抑制。例如，丝状真菌Aspergillus flavus的全基因组中预测存在30种以上次级代谢产物生物合成基因簇，但实际上只有少数几种被识别。在许多情况下，大多数生物合成基因处于休眠状态，并不能确认生产天然产物。通过异源表达方式，不仅可以解明已知天然产物的生物合成途径，还可以通过激活具有潜在功能的基因簇，挖掘新的代谢产物。

研究方向三：高效合成具有应用价值的化合物：

“合成生物学”理论和技术极大的推动了生物技术领域的发展，被意为可改变世界的十大新技术之一，是影响未来的颠覆性技术，极大的促进了生物制造领域的创新发展。通过我们对基因的挖掘，明确酶的功能和反应机理，将来可以定向的对酶进行改造，将不同来源的生物相关代谢途径模块化，并在底盘上进行组装，设计合适的生物合成路径，提高代谢途径的效率，降低大规模生物催化反应的成本，实现各种重要次级代谢产物高效生物合成和规模化生产。

教学情况:

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基金评审经历:

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近年承担的主要课题:

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主要发表文章: (近五年)

1. Lei Gao, Cong Su, Xiaoxia Du, Ruishan Wang, Shuming Chen, Yu Zhou,Chengwei Liu, Xiaojing Liu, Runze Tian, Liyun Zhang, Kebo Xie, She Chen, Qianqian Guo, Lanping Guo, Yoshio Hano, Manabu Shimazaki, Atsushi Minami, Hideaki Oikawa, Niu Huang, K N Houk, Luqi Huang*, Jungui Dai*, Xiaoguang Lei*. FAD-dependent enzyme-catalysed intermolecular [4+2] cycloaddition in natural product biosynthesis.NatChem., 12(7), 620-628, 2020. doi: 10.1038/s41557-020-0467-7.

2. Yulu Jiang, Taro Ozaki, Mei Harada, Tadachika Miyasaka, Hajime Sato, Kazunori Miyamoto, Junichiro Kanazawa,Chengwei Liu, Jun-Ichi Maruyama, Masaatsu Adachi, Atsuo Nakazaki, Toshio Nishikawa, Masanobu Uchiyama, Atsushi Minami, Hideaki Oikawa*. Biosynthesis of Indole Diterpene Lolitrems: Radical-Induced Cyclization of an Epoxyalcohol Affording a Characteristic Lolitremane Skeleton.Angew Chem Int Ed Engl., 59, 17996-18002, 2020. doi: 10.1002/anie.202007280.

3. Tetsuya Shiina, Taro Ozaki, Yusuke Matsu, Shota Nagamine,Chengwei Liu, Masaru Hashimoto, Atsushi Minami, Hideaki Oikawa*. Oxidative Ring Contraction by a Multifunctional Dioxygenase Generates the Core Cycloocatadiene in the Biosynthesis of Fungal Dimeric Anhydride Zopfiellin.Org Lett.,22(5),1997-2001, 2020. doi: 10.1021/acs.orglett.0c00340.

4. Chengwei Liu, Atsushi Minami, Taro Ozaki, Jing Wu, Hirokazu Kawagishi, Jun-ichi Maruyama, Hideaki Oikawa*. Efficient reconstitution of Basidiomycota diterpene erinacine gene cluster in Ascomycota hostAspergillus oryzaebased on genomic DNA sequences.J. Am. Chem. Soc.,141 (39), 15519-15523,2019. doi: 10.1021/jacs.9b08935.

5. Shota Nagamine,Chengwei Liu, Jumpei Nishishita, Takuto Kozaki, Kaho Sogahata, Yoshiro Sato, Atsushi Minami, Taro Ozaki, Claudia Schmidt-Dannert, Jun-ichi Maruyama, Hideaki Oikawa*. Ascomycota Aspergillus oryzae is an efficient expression host for production of Basidiomycota terpenes using genomic DNA sequences.Appl Environ Microbiol.,85 (15), e00409-19, 2019. doi: 10.1128/AEM.00409-19.

6. Takahiro Ugai, Atsushi Minami，Shizuya Tanaka，Taro Ozaki，Chengwei Liu，Hideyuki Shigemori，Masaru Hashimoto, Hideaki Oikawa*. Biosynthetic machinery of 6‐hydroxymellein derivatives leading to cyclohelminthols and palmaenones.ChemBioChem.21 (3), 360-367,2020. doi: 10.1002/cbic.201900404.

7. Junya Takino, Takuto Kozaki, Taro Ozaki,Chengwei Liu, Atsushi Minami, Hideaki Oikawa*. Elucidation of biosynthetic pathway of a plant hormone abscisic acid in phytopathogenic fungi.Biosci. Biotech. Biochem.83 (9), 1642-1649, 2019. DOI: 10.1080/09168451.2019.1618700.

8. Ying Ye, Taro Ozaki, Myco Umemura,Chengwei Liu, Atsushi Minamia, Hideaki Oikawa*. Heterologous production of asperipin-2a: proposal for sequential oxidative macrocyclization by a fungi-specific DUF3328 oxidase.Org Biomol Chem., 17(1), 39-43, 2019. doi: 10.1039/c8ob02824a.

9. Atsushi Minami*, Taro Ozaki,Chengwei Liu, Hideaki Oikawa*. Cyclopentane-forming di/sesterterpene synthases: widely distributed enzymes in bacteria, fungi, and plants.Nat Prod Rep. 35 (12), 1330-1346, 2018. doi: 10.1039/c8np00026c.

10. Tetsuya Shiina, Kazuya Nakagawa, Yukiko Fujisaki, Taro Ozaki,Chengwei Liu, Tomonobu Toyomasu, Masaru Hashimoto, Hiroyuki Koshino, Atsushi Minami, Hiroshi Kawaide & Hideaki Oikawa*. Biosynthetic study of conidiation-inducing factor conidiogenone: heterologous production and cyclization mechanism of a key bifunctional diterpene synthase.Biosci Biotechnol Biochem.83 (2), 192-201,2019. doi: 10.1080/09168451.2018.1536518.

11. Junya Takino, Takuto Kozaki, Yoshiro Sato,Chengwei Liu, Taro Ozaki, Atsushi Minami*, Hideaki Oikawa*. Unveiling Biosynthesis of the Phytohormone Abscisic Acid in Fungi: Unprecedented Mechanism of Core Scaffold Formation Catalyzed by an Unusual Sesquiterpene Synthase.J. Am. Chem. Soc.,140 (39), 12392-12395, 2018. doi: 10.1021/jacs.8b08925.

12. Akihiro Tazawa, Ying Ye, Taro Ozaki,Chengwei Liu, Yasushi Ogasawara, Tohru Dairi, Yusuke Higuchi, Nobuo Kato, Katsuya Gomi, Atsushi Minami, and Hideaki Oikawa*. Total Biosynthesis of Brassicicenes: Identification of a Key Enzyme for Skeletal Diversification.Org. Lett.20 (19), 6178-6182, 2018. doi: 10.1021/acs.orglett.8b02654.

13. Kosei Kudo,Chengwei Liu, Tomoyuki Matsumoto, Atsushi Minami, Taro Ozaki, Hiroaki Toshima, Katsuya Gomi, Hideaki Oikawa. Heterologous biosynthesis of fungal indole sesquiterpene sespendole.Chembiochem.19 (14), 1492-1497, 2018. doi: 10.1002/cbic.201800187.

14. Taro Ozaki, Sandip S. Shinde, Lei Gao, Ryo Okuizumi,Chengwei Liu,Yasushi Ogasawara, Xiaoguang Lei, Tohru Dairi, Atsushi Minami, Hideaki Oikawa*.Enzymatic formation of a skipped methyl‐substituted octaprenyl side chain of longestin (KS‐505a): Involvement of homo‐IPP as a common extender unit.Angew. Chem. Int. Ed. Engl.57 (22), 6629-6632,2018. doi: 10.1002/anie.201802116.

15. Koji Narita, Atsushi Minami, Taro Ozaki,Chengwei Liu, Motoichiro Kodama, Hideaki Oikawa*. Total Biosynthesis of Antiangiogenic Agent (−)-Terpestacin by Artificial Reconstitution of the Biosynthetic Machinery in Aspergillus oryzae.

J. Org. Chem.83(13), 7042-7048. 2018. doi: 10.1021/acs.joc.7b03220.

16. Lei Gao, Koji Narita, Taro Ozaki, Naoyoshi Kumakura, Pamela Gan, Atsushi Minami,Chengwei Liu, Xiaoguang Lei, Ken Shirasu, Hideaki Oikawa*. Identification of novel sesterterpenes by genome mining of phytopathogenic fungiPhomaandColletotrichumsp.Tetrahedron Letters. 59 (12), 1136-1139, 2018.

17. Momoka Yamane, Atsushi Minami,Chengwei Liu, Taro Ozaki, Ichiro Takeuchi, Tae Tsukagoshi, Tetsuo Tokiwano, Katsuya Gomi, Hideaki Oikawa*. Biosynthetic machinery of diterpene pleuromutilin isolated from basidiomycete fungi.Chembiochem. 18 (23), 2317-2322, 2017. doi: 10.1002/cbic.201700434.

18. Koji Narita, Hajime Sato, Atsushi Minami, Kosei Kudo, Lei Gao,Chengwei Liu, (他8人). Focused Genome Mining of Structurally Related Sesterterpenes: Enzymatic Formation of Enantiomeric and Diastereomeric Products.Org. Lett. 19 (24), 6696–6699, 2017. doi: 10.1021/acs.orglett.7b03418.

19. Chengwei Liu, Atsushi Minami, Tohru Dairi, Katsuya Gomi, Barry Scott, Hideaki Oikawa*. Biosynthesis of Shearinine: Diversification of a Tandem Prenyl Moiety of Fungal Indole Diterpenes.Org. Lett.18 (19), 5026-5029, 2016. DOI: 10.1021/acs.orglett.6b02482.

20. Atsushi Minami,Chengwei Liu, Hideaki Oikawa*. Total Biosynthesis of Fungal Indole Diterpenes Using Cell Factories.Heterocycles.92 (3), 397-421, 2016.

21. Chengwei Liu, Koichi Tagami, Atsushi Minami, Tomoyuki Matsumoto, Jens Christian Frisvad, Hideyuki Suuki, Jun Ishikawa, Katsuya Gomi, Hideaki Oikawa*. Reconstitution of Biosynthetic Machinery for the Synthesis of the Highly Elaborated Indole Diterpene Penitrem.Angew. Chem. Int. Ed. Engl. 54 (19), 5748-52, 2015. DOI: 10.1002/anie.201501072. (Hot Paper, Cover Picture)

22. Ying Ye, Atsushi Minami, Attila Mandi,Chengwei Liu, Tohru Taniguchi, Tomohisa Kuzuyama, Kenji Monde, Katsuya Gomi, and Hideaki Oikawa*. Genome Mining for Sesterterpenes Using Bifunctional Terpene Synthases Reveals a Unified Intermediate of Di/Sesterterpenes.Am. Chem. Soc.137(36), 11846-53, 2015. doi: 10.1021/jacs.5b08319.

23. 南篤志,尾崎太郎,劉成偉,及川英秋.

糸状菌による植物ホルモンアブシジン酸の生合成・新奇な環化酵素の発見. バイオサイエンスとインダストリー,77(2), 136-138, 2019.

24. 南篤志,尾崎太郎,劉成偉,及川英秋.

糸状菌テルペン環化酵素遺伝子のゲノムマイニングによる新規天然物の生産.バイオサイエンスとインダストリー,76(1), 20-25, 2018.

25. 南篤志,劉成偉,及川英秋.

麹菌異種発現系を利用した糸状菌由来天然物の生産.

バイオサイエンスとインダストリー,73(6), 467-470, 2015.

2014年以前论文：

26. Chengwei Liu, Motoyoshi Noike, Atsushi Minami, Hideaki Oikawa, Tohru Dairi*. A fungal prenyltransferase catalyzes the regular di-prenylation at positions 20 and 21 of paxilline.Biosci. Biotechnol. Biochem.78 (4), 448-54, 2014. doi:10.1080/09168451.2014.882759. doi:10.1080/09168451.2014.882759.

27. Chengwei Liu, Motoyoshi Noike, Atsushi Minami, Hideaki Oikawa, Tohru Dairi*. Functional analysis of a prenyltransferase gene (paxD) in the paxilline biosynthetic gene cluster.Appl. Microbiol. Biotechnol.98 (1), 199-06, 2014. DOI:10.1007/s00253-013-4834-9. doi: 10.1007/s00253-013-4834-9.

28. Koichi Tagami, Atsushi Minami, Ryuya Fujii,Chengwei Liu, Mizuki Tanaka, Katsuya Gomi, Tohru Dairi, Hideaki Oikawa. Rapid Reconstitution of Biosynthetic Machinery for Fungal Metabolites in Aspergillus oryzae: Total Biosynthesis of Aflatrem.ChemBioChem.15(14), 2076-80, 2014. doi: 10.1002/cbic.201402195.

29. Chengwei Liu, Atsushi Minami, Motoyoshi Noike, Hiroaki Toshima, Hideaki Oikawa, Tohru Dairi*. Regiospecificities and prenylation mode specificities of the fungal indole diterpene prenyltransferases AtmD and PaxD.Appl. Environ. Microbiol.79 (23), 7298-304, 2013. doi: 10.1128/AEM.02496-13. doi: 10.1128/AEM.02496-13.

30. Koichi Tagami,Chengwei Liu, Atsushi Minami, Motoyoshi Noike, Tetsuya Isaka, Shuhei Fueki, Yoshihiro Shichijo, Hiroaki Toshima , Katsuya Gomi, Tohru Dairi, Hideaki Oikawa. Reconstitution of Biosynthetic Machinery for Indole-Diterpene Paxilline inAspergillus oryzae.J. Am. Chem. Soc.135 (4), 1260–63, 2013. doi: 10.1021/ja3116636.

31. Xiaodong Ding, Tadashi Matsumoto, Patrizia Gena,Chengwei Liu, Marialuisa Pellegrini-Calace, Shihua Zhong, Xiaoli Sun, Yanming Zhu, Maki Katsuhara, Ikuko Iwasaki, Yoshichika Kitagawa, Giuseppe Calamita. Water and CO₂permeability of SsAqpZ, the cyanobacterium Synechococcus sp. PCC7942 aquaporin.Biol. Cell.105 (3), 118-128, 2013. doi: 10.1111/boc.201200057.

32. Chengwei Liu, Tatsuya Fukumoto, Tadashi Matsumoto, Patrizia Gena, Daniele Frascaria, Tomoyuki Kaneko, Maki Katsuhara, Shihua Zhong, Xiaoli Sun, Yanming Zhu, Ikuko Iwasaki, Xiaodong Ding, Giuseppe Calamita*, Yoshichika Kitagawa*. Aquaporin OsPIP1;1 promotes rice salt resistance and seed germination.Plant. Physiol. Biochem.63, 151-158, 2013. doi:10.1016/j.plaphy.2012.11.018.

33. Motoyoshi Noike,Chengwei Liu, Yusuke Ono, Yoshimitsu Hamano, Tomonobu Toyomasu, Takeshi Sassa, Nobuo Kato, Tohru Dairi*. An Enzyme Catalyzing O-Prenylation of the Glucose Moiety of Fusicoccin A, a Diterpene Glucoside Produced by the FungusPhomopsis amygdali.ChemBioChem.13 (4), 566-73, 2012. doi: 10.1002/cbic.201100725.

34. Yoshichika Kitagawa*,Chengwei Liu, Xiaodong Ding*. The influence of natural mineral water on aquaporin water permeability and human natural killer cell activity.Biochem. Biophys. Res. Commun.409 (1), 40-5, 2011. doi: 10.1016/j.bbrc.2011.04.102.

35. Tadashi Matsumoto, Hong-Li Lian, Wei-Ai Su, Daisuke Tanaka,Chengwei Liu,Ikuko Iwasaki, Yoshichika Kitagawa*. Role of the aquaporin PIP1 subfamily in the chilling tolerance of rice.Plant. Cell. Physiol.50 (2), 216-29, 2009. doi: 10.1093/pcp/pcn190.

36. 劉成偉,松本直，岩崎郁子，北川良親*.

アクアポリンの水透過性と植物のストレス耐性に対する日田天領水の作用.Food Style.13 (1), 92-97, 2009.