本课题组主要应用代谢工程、合成生物学与系统生物学的原理和方法，通过先进基因工程手段操纵微生物代谢，提升有用的化学品（包括生物燃料、聚合物单体、医药与食品高值分子等）的合成效率，以达到产业应用水平；同时组合多种组学分析、生物信息学、计算设计和蛋白结构分析等，实现多维度、跨尺度的微生物设计和改造，构建智能化的微生物细胞工厂。

团队成员在脂类代谢工程与系统生物学研究领域，发表学术论文20余篇，包括在Nature Catalysis, Nature Chemical Biology, Nature Communications, PNAS等杂志发表第一作者论文多篇，总被引用次数超1200次，h-index 14（基于Google Scholar统计数据）；申请国内外专利4项，其中国内授权3项，国际PCT专利授权1项。曾荣获得大连市技术发明一等奖、15届国际生物技术大会（International Biotechnology Symposium，IBS2012）最佳墙报奖等，并在国内外学术会议做口头报告或墙报展示10多次。

重设计真菌脂肪酸合酶（Fatty acid synthase）合成非天然的产物，打破了该酶无法被改造的传统观念，开创了使用真菌脂肪酸合酶生产化学品和生物燃料的新思路。该工作以封面故事的形式发表于Nature Chemical Biology杂志，并受到30多家媒体的关注和报道，相关专利转让给法国道达尔（TOTAL）公司。提出“多维代谢工程”概念，并指导改造酵母合成高值中链脂肪酸及其衍生物，使中链脂肪酸的产量提高250倍以上，相关论文被Nature Catalysis杂志发表，并受到生物技术权威综述杂志Treads in Biotechnology报道和推荐。

近期代表性论文（# 第一作者，* 通讯作者）

1. Zhiwei Zhu#, Yating Hu#, Paulo G. Teixeira, Rui Pereira, Yun Chen, Verena Siewers & Jens Nielsen*. (2020). Multidimensional engineering of Saccharomyces cerevisiae for efficient synthesis of medium-chain fatty acids. Nature Catalysis, 3(1), 64-74. doi:10.1038/s41929-019-0409-1

Highlight by Jianhui Liu & Jin Hou. (2020). Multidimensional Metabolic Engineering for Constructing Efficient Cell Factories. Trends in Biotechnology, 38(5), 468-469. doi:10.1016/j.tibtech.2020.02.011

2. Zhiwei Zhu, Yongjin J. Zhou, Anastasia Krivoruchko, Martin Grininger, Zongbao K. Zhao* & Jens Nielsen*. (2017). Expanding the product portfolio of fungal type I fatty acid synthases. Nature Chemical Biology, 13(4), 360-362. doi:10.1038/nchembio.2301

Cover story, News and Views by Timm Maier. (2017). Fatty acid synthases: Re-engineering biofactories. Nature Chemical Biology, 13(4), 344-345. doi:10.1038/nchembio.2338

3. Zhiwei Zhu, Sufang Zhang, Hongwei Liu, Hongwei Shen, Xinping Lin, Fan Yang, Yongjin J. Zhou, Guojie Jin, Mingliang Ye, Hanfa Zou* & Zongbao K. Zhao*. (2012). A multi-omic map of the lipid-producing yeast Rhodosporidium toruloides. Nature Communications, 3, 1112. doi:10.1038/ncomms2112

4. Yating Hu#, Zhiwei Zhu#, David Gradischnig, Margit Winkler, Jens Nielsen* & Verena Siewers. (2020). Engineering carboxylic acid reductase for selective synthesis of medium-chain fatty alcohols in yeast. Proceedings of the National Academy of Sciences, 202010521. doi:10.1073/pnas.2010521117

5. Zhiwei Zhu, Yongjin J. Zhou, Min-Kyoung Kang, Anastasia Krivoruchko, Nicolaas A. Buijs & Jens Nielsen*. (2017). Enabling the synthesis of medium chain alkanes and 1-alkenes in yeast. Metabolic Engineering, 44, 81-88. doi:10.1016/j.ymben.2017.09.007

1. 赵宗保, 朱志伟, 张素芳. 一种产油酵母脂肪酸合酶及其编码基因与应用. 中国专利授权号: ZL201310067825.0 申请日: 2010-06-02 授权日: 2013-05-15

2. 赵宗保, 朱志伟, 张素芳. 一种产油酵母脂滴蛋白及其编码基因与应用. 中国专利授权号: 201310039949.8 申请日: 2013-01-31 授权日: 2016-06-29

3. 张素芳, 赵宗保, 朱志伟. 果糖-1,6-二磷酸醛缩酶启动子及应用和构建体、载体. 中国专利授权号: ZL201010189723.2 申请日: 2013-03-04 授权日: 2016-07-27

4. Zhiwei Zhu, Anastasia Krivoruchko, Jens Nielsen. 2016. Method of producing fatty acids. 美国国专利授权号: US10648043B2 申请日: 2016-03-04 授权日: 2020-05-12

Web of Science 引用情况：

Google Scholar 引用情况：

2020

22. Yating Hu#, Zhiwei Zhu#, David Gradischnig, Margit Winkler, Jens Nielsen* & Verena Siewers. (2020). Engineering carboxylic acid reductase for selective synthesis of medium-chain fatty alcohols in yeast. Proceedings of the National Academy of Sciences, 202010521. doi:10.1073/pnas.2010521117

21. Renhui Zhou#, Zhiwei Zhu#, Sufang Zhang* & Zongbao K. Zhao. (2020). The complete mitochondrial genome of the lipid-producing yeast Rhodotorula toruloides. FEMS Yeast Research. doi:10.1093/femsyr/foaa048

20. Zhiwei Zhu#, Yating Hu#, Paulo G. Teixeira, Rui Pereira, Yun Chen, Verena Siewers & Jens Nielsen*. (2020). Multidimensional engineering of Saccharomyces cerevisiae for efficient synthesis of medium-chain fatty acids. Nature Catalysis, 3(1), 64-74. doi:10.1038/s41929-019-0409-1

2019

19. Yating Hu, Zhiwei Zhu, Jens Nielsen* & Verena Siewers. (2019). Engineering Saccharomyces cerevisiae cells for production of fatty acid derived biofuels and chemicals. Open Biology, 9(5), 190049. doi:10.1098/rsob.190049

2018

18. Yongjin J. Zhou*, Yating Hu, Zhiwei Zhu, Verena Siewers & Jens Nielsen*. (2018). Engineering 1-Alkene Biosynthesis and Secretion by Dynamic Regulation in Yeast. ACS Synthetic Biology, 7(2), 584-590. doi:10.1021/acssynbio.7b00338

17. Yanan Wang, Sufang Zhang*, Zhiwei Zhu, Hongwei Shen, Xinping Lin, Xiang Jin, Xiang Jiao & Zongbao K. Zhao*. (2018). Systems analysis of phosphate-limitation-induced lipid accumulation by oleaginous yeasts Rhodosporidium toruloides. Biotechnology for Biofuels, 11, 148. doi:10.1186/s13068-018-1134-8

16. Yating Hu, Zhiwei Zhu, Jens Nielsen & Verena Siewers*. (2018). Heterologous transporter expression for improved fatty alcohol secretion in yeast. Metabolic Engineering, 45, 51-58. doi:10.1016/j.ymben.2017.11.008

2017

15. Zhiwei Zhu, Yongjin J. Zhou, Anastasia Krivoruchko, Martin Grininger, Zongbao K. Zhao* & Jens Nielsen*. (2017). Expanding the product portfolio of fungal type I fatty acid synthases. Nature Chemical Biology, 13(4), 360-362. doi:10.1038/nchembio.2301

14. Zhiwei Zhu, Yongjin J. Zhou, Min-Kyoung Kang, Anastasia Krivoruchko, Nicolaas A. Buijs & Jens Nielsen*. (2017). Enabling the synthesis of medium chain alkanes and 1-alkenes in yeast. Metabolic Engineering, 44, 81-88. doi:10.1016/j.ymben.2017.09.007

2016

13. Yongjin J. Zhou, Nicolaas A. Buijs, Zhiwei Zhu, Jiufu Qin, Verena Siewers & Jens Nielsen*. (2016). Production of fatty acid-derived oleochemicals and biofuels by synthetic yeast cell factories. Nature Communications, 7, 11709. doi:10.1038/ncomms11709

12. Yongjin J. Zhou* #, Nicolaas A. Buijs#, Zhiwei Zhu, Diego Orol Gómez, Akarin Boonsombuti, Verena Siewers & Jens Nielsen*. (2016). Harnessing Yeast Peroxisomes for Biosynthesis of Fatty-Acid-Derived Biofuels and Chemicals with Relieved Side-Pathway Competition. Journal of the American Chemical Society, 138(47), 15368-15377. doi:10.1021/jacs.6b07394

2015

11. Zhiwei Zhu#, Yunfeng Ding#, Zhiwei Gong, Li Yang, Sufang Zhang, Congyan Zhang, Xinping Lin, Hongwei Shen, Hanfa Zou, Zhensheng Xie, Fuquan Yang, Xudong Zhao, Pingsheng Liu* & Zongbao K. Zhao*. (2015). Dynamics of the Lipid Droplet Proteome of the Oleaginous Yeast Rhodosporidium toruloides. Eukaryotic Cell, 14(3), 252-264. doi:10.1128/ec.00141-14

10. Manuel Fischer, Daniel Rhinow, Zhiwei Zhu, Deryck J. Mills, Zongbao K. Zhao, Janet Vonck & Martin Grininger*. (2015). Cryo-EM structure of fatty acid synthase (FAS) from Rhodosporidium toruloides provides insights into the evolutionary development of fungal FAS. Protein Science, 24(6), 987–995. doi:10.1002/pro.2678

2014

9. 朱志伟, 张素芳, 林心萍, 刘武军 & 赵宗保*. (2014). 圆红冬孢酵母新颖脂肪酸合酶的重组表达、纯化与活性检测. 生物工程学报, 30(9), 1414–1423. doi:10.13345/j.cjb.130626

8. 刘玉雪, 张祎昕, 王磊, 林心萍, 朱志伟 & 赵宗保*. (2014). 重组酿酒酵母催化二氢大豆苷元生产雌马酚. 中国生物工程杂志, 34(4), 41-45. doi:10.13523/j.cb.20140407

7. Xinping Lin, Yanan Wang, Sufang Zhang, Zhiwei Zhu, Yongjin J. Zhou, Fan Yang, Wenyi Sun, Xueying Wang & Zongbao K. Zhao*. (2014). Functional integration of multiple genes into the genome of the oleaginous yeast Rhodosporidium toruloides. FEMS Yeast Research, 14(4), 547-555. doi:10.1111/1567-1364.12140

2013

6. Yongjin J. Zhou, Wei Yang, Lei Wang, Zhiwei Zhu, Sufang Zhang & Zongbao K. Zhao*. (2013). Engineering NAD+ availability for Escherichia coli whole-cell biocatalysis: a case study for dihydroxyacetone production. Microbial Cell Factories, 12(1), 103. doi:10.1186/1475-2859-12-103

5. 蔡媛, 郭娟, 周雍进, 朱志伟, 吴文燕, 黄璐琦, 陈敏*, & 赵宗保. (2013). 转化次丹参酮二烯酿酒酵母全细胞催化体系的构建. 药学学报, 48(10), 1618-1623.

2012

4. Zhiwei Zhu, Sufang Zhang, Hongwei Liu, Hongwei Shen, Xinping Lin, Fan Yang, Yongjin J. Zhou, Guojie Jin, Mingliang Ye, Hanfa Zou* & Zongbao K. Zhao*. (2012). A multi-omic map of the lipid-producing yeast Rhodosporidium toruloides. Nature Communications, 3, 1112. doi:10.1038/ncomms2112

3. Yongjin J. Zhou#, Wei Gao#, Qixian Rong, Guojie Jin, Huiying Chu, Wujun Liu, Wei Yang, Zhiwei Zhu, Guohui Li, Guofeng Zhu, Luqi Huang*, & Zongbao K. Zhao*. (2012). Modular pathway engineering of diterpenoid synthases and the mevalonic acid pathway for miltiradiene production. Journal of the American Chemical Society, 134(6), 3234–3241. doi:10.1007/s00253-011-3820-3

2. Fan Yang, Sufang Zhang, Yongjin J. Zhou, Zhiwei Zhu, Xinping Lin, & Zongbao K. Zhao*. (2012). Characterization of the mitochondrial NAD+-dependent isocitrate dehydrogenase of the oleaginous yeast Rhodosporidium toruloides. Applied Microbiology and Biotechnology, 94(4), 1095-1105. doi:10.1007/s00253-011-3820-3

1. Xinping Lin, Fan Yang, Yongjin Zhou, Zhiwei Zhu, Guojie Jin, Sufang Zhang*, & Zongbao K. Zhao. (2012). Highly-efficient colony PCR method for red yeasts and its application to identify mutations within two leucine auxotroph mutants. Yeast, 29(11), 467-474. doi:10.1002/yea.2926

朱志伟 博士 教授

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