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.
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.
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.
Ongoing grants
1. Outstanding Young Scholar Fund of NSFC: Designing efficient microbial cell factories (22425807, 2025-2029), CNY 4,000,000, PI: Yongjin Zhou
2. Main program of NSFC: Synergistic utilization of multiple carbon sources from lignocellulosic hydrolysates for efficient bio-manufacturing (22478382,2025-2028), CNY 500,000, PI: Jiaoqi Gao
3. Main program of NSFC: Non-natural coenzyme mediated and formate regulated biosynthesis of 1,3-propanediol from glycerol (22377125, 2024-2027), CNY 500,000, PI: Xueying Wang
4. Youth program of NSFC: De novo biosynthesis of (+)-nootkatone in engineered Ogataea polymorpha and its regulatory mechanisms (22407122, 2025-2027), CNY 300,000, PI: Fei Yu
5. Youth program of NSFC: Multi-omics analysis of tolerance and metabolism mechanism of high concentration methanol in Pichia pastoris (22308352, 2024-2026), CNY 300,000, PI: Peng Cai
6. National Key Research and Development Project: Design and construction of natural rubber pathway in cell factory (2023YFA0914800, 2023-2028), CNY 1,150,000, Co-PI: Ning Gao
7. National Key Research and Development Project: Enhancing carbon fixation process by multi-enzyme catalysis (2022YFC2105900, 2023-2026), CNY 2,200,000, Co-PI: Yunxia Li
8. National Key Research and Development Project: Development of synthetic biology system to produce bioactive terpenoids (2023YFC3503900, 2023-2026), CNY 660,000, Co-PI: Fan Bai
9. National Key Research and Development Project: Construction and adaptation mechanisms of artificial biological systems (2022YFA0912000, 2023-2027), CNY 800,000, Co-PI: Xueying Wang
10. Strategic Priority Research Program of the Chinese Academy of Sciences: Methanol to formaldehyde and hydrogen production (XDC0120102, 2023-2026), CNY1,000,000, Co-PI: Xueying Wang
11. Key project at central government level/The ability establishment of sustainable use for valuable Chinese medicine resources: Biosynthesis of complex active ingredients from Chinese medicine by synthetic yeast consortia (2060302-2401-10, 2024-2026), CNY 2,600,000, PI: Yongjin Zhou
12. Key project at central government leve/The ability establishment of sustainable use for valuable Chinese medicine resources: Biosynthesis of active sesquiterpenes from Chinese medicine by Ogataea polymorpha (2060302-2302-11, 2023-2025), CNY 600,000, PI: Jiaoqi Gao
13. China Postdoctoral Science Foundation (2021-2025), CNY 80,000, PI: Peng Cai
14. Dalian Science and Technology Innovation Funding: Methanol biotransformation for 3-hydroxypropionic acid production (2022RJ17, 2023-2025), CNY1,000,000, PI: Yongjin Zhou
15. Innovation Foundation of Dalian Institute of Chemical Physics, CAS: Methanol biotransformation toward single cell protein by Pichia pastoris (DICP I202466, 2025-2026), CNY 1,000,000, PI: Fan Bai