Research

Methanol Biotransformation


Bio-manufacture is considered as a green and sustainable route for future energy and chemical supply, and current biorefinery mainly uses biomass derived sugars as feedstock. However, the soaring demand calls the expanding the feedstock resources and the plenty of natural gas and low quality coal might contribute to future energy supply. Instead of direct combustion with high pollution, transformation the coal to methanol for chemical industry is a feasible approach. In addition, methanol can be large-scaled prepared from CO2 hydrogenation. Therefore, methanol can be employed as a potential raw material for bio-refinery. Our lab is devoted to engineer microbes, in particular methylotrophic yeast, to transform methanol toward bulk chemicals and high quality biofuels. 


Development of Synthetic Biology Tools


It is challenging in engieering non-conventional methylotrophic yeasts (such as Komagataella phaffii and Hansenula polymorpha) due to serious lack of genetic editing tools in compared with the modeling yeast Saccharomyces cerevisiae with numerous advanced genetic tools and biological devices. In particular, non-homology end joining (NHEJ) is the domain at DNA repair system in non-conventional methylotrophic yeasts, which hinders their precise genetic engineering. We are focusing on optimizing the CRISPR-Cas9 gene editing system and engineering recombination machinery in methylotrophic yeasts. Furthermore, we are trying to characterize the essential biological elements such as methanol responsive promoters and neutral sites for construction of smart biosynthetic pathways in methylotrophic yeasts. Some novel synthetic biology tools will be also implemented in model yeast S. cerevisiae.


Microbial synthesis of natural products


Plant natural products have been utilized for millennia as pharmaceuticals, flavors, and fragrances, along with other industrial uses. However, due to the structural complexity, low volume and limited resource, traditional plant extraction can not meet the current demands. Synthetic biology can help to harness microbes for high-level production of natural products within weeks at an environmentally friendly manner. We are engineering yeast cell factories for producing several natural products that can be used as pharmaceuticals, cosmetics and flavors.


Projects

Ongoing

1. National Talent Programme for Young Scientists. Engineering of microbial cell factory (2018-2022), ¥3,000,000, PI: Yongjin Zhou

2. National Key Research and Development Project. Mining and analysis of key functional gene modules (2018YFA0900302, 2019-2024), ¥1,470,000, PI: Yongjin Zhou

3. National Key Research and Development Project. The design and construction of efficient microbial cell factories (2021YFC2100500, 2021-2024), ¥2,120,000, Co-PI: Yongjin Zhou, Hongwei Luan

4. National Key Research and Development Project. Integration of ionic enzymes and microbial cells for production of fatty acids from CO2 (2021YFC2104200, 2021-2024), ¥900,000, PI: Jiaoqi Gao

5. National Key Research and Development Project. Production of biofuels and biochemical from C1 feedstocks (2021YFC2103500, 2021-2024), ¥1,800,000, Co-PI: Lun Yao, Hongwei Luan

6. DMTO Research Grant of Dalian Institute of Chemical Physics, CAS. Research on methanol biotransformation and its mechanisms (DICP DMTO201701, 2018-2022), ¥3,000,000, PI:Yongjin Zhou

7. Innovation Foundation of Dalian Institute of Chemical Physics, CAS. Synthetic biology research guided by biocatalysis (2017-2022), ¥5,000,000, PI: Yongjin Zhou

8. Innovation Foundation of Dalian Institute of Chemical Physics, CAS. Efficient production of anti-cancer drug β-elemene by Ogataea polymorpha (DICP I202021, 2020-2022), ¥1,000,000, PI:Jiaoqi Gao

9. Innovation Foundation of Dalian Institute of Chemical Physics, CAS. Improvement of methanol metabolism and investigation of its regulation in Pichia pastoris (DICP I202111,2022-2023), ¥1,000,000, PI: Lun Yao

National NaturalScience Foundation of China

1. Excellent Youth Program of NSFC. Construction andoptimizationof microbial cell reactor (21922812, 2020-2022), ¥1,200,000, PI: Yongjin Zhou

2. Cooperation Program of NSFC. Co-utilization of methanol and sugarcane hydrolysates for production of fatty acid derivatives (22161142008,2021-2023), ¥1,990,000,  PI: YongjinZhou

3. Sino-German Mobility Program of NSFC. Compartmentalized synthesis of fatty acids and alcohols with various chain lengths from methanol (M-0246,2021-2023), ¥681,000, PI: Yongjin Zhou

4. National Natural Science Foundation of China (NSFC). Spatiotemporal regulation of peroxisomal fattyacid metabolism for biosynthesis of fatty alcohols (21877111, 2019-2022), ¥670,000, PI: Yongjin Zhou

Completed

1. Youth Fund Project of NSFC. Regulation of acetyl-coA biosynthesis in Pichia pastoris (31700082, 2018-2020), ¥250,000, PI: Yongjin Zhou

2. Youth Fund Project of NSFC. Molecular basis on methanol metabolism by Hansenula polymorpha (21808216, 2019-2021), ¥260,000, PI: Jiaoqi Gao

3.Youth Fund Project of NSFC. Study on the metabolic regulation of Farnesyl pyrophosphate in Pichia pastoris (21807100, 2019-2021), ¥250,000, PI: Xingpeng Duan

4. China Postdoctoral Science Foundation. Enhancing sclareol production by engineering yeast Saccharomyces cerevisiae (199936, 2018-2019), ¥50,000, PI: Xuan Cao

5.Talent Project of Revitalizing Liaoning. Talent project of revitalizing Liaoning for Distinguished Young Scholar (2019-2021), ¥500,000, PI: Yongjin Zhou

6. Dalian Science and Technology Innovation Fund. Methanol biotransformation for production of fatty alcohols (2019J12GX030,2020-2021), ¥500,000, PI: Yongjin Zhou

7. Young Talents Program of The Chinese Academy of Sciences. Design and optimization of microbial cell factories (2018-2019), ¥1,300,000, PI: Yongjin Zhou

8. Regional Key Projects of CAS Science and Technology Service Network Initiative.Establishment of Dandong berry processing platform and development of Actinidia arguta processing products (KFJ-STS-QYZD-191, 2020-2021),¥2,000,000, PI: Hongwei Luan

9. Innovation Foundation of Dalian Institute of Chemical Physics, CAS. Methanol biotransformation for production of 3-hydroxypropionic acid (DICP I201920,2019-2021), ¥1,000,000, PI:YongjinZhou