总监

I. Job Responsibilities

1. Enzyme Catalyst Design and Development

For target chemical reactions (including chiral synthesis, drug intermediate conversion, antibody conjugation, etc.), design or screen enzyme catalysts with high catalytic activity, high selectivity (stereospecific/areal/chemical selectivity) and high stability from scratch;

Establish an enzyme-substrate/product tolerance assessment system to solve key engineering problems such as substrate inhibition, product toxicity, and organic solvent tolerance;

Output scalable enzyme catalytic solutions to support the pipeline transition from mg-level to kg-level processes.

2. Enzyme Directed Evolution and High-throughput Screening

Independently build and continuously optimize directed evolution technology platforms (misfolded PCR, DNA shuffling, saturation mutagenesis, CAST/ISM combination mutation strategies, etc.);

Establish high-throughput screening methods (spectroscopy, fluorescence, HPLC/UPLC linkage, microplate activity detection, etc.) to achieve rapid screening of 10³–10⁴ mutant levels per day;

Lead in hotspot residue localization, mutation combination design and performance iteration, and complete multiple rounds of evolution to increase enzyme activity, stability, selectivity, etc. by 10–1000 times or more.

3. Enzyme Structure Simulation and Rational Modification

Utilize computational methods such as molecular docking (AutoDock/Schrodinger), molecular dynamics simulation (AMBER/GROMACS), QM/MM, DFT, etc. to analyze the catalytic mechanism and substrate recognition mode of enzymes;

Combine sequence-structure-function relationships to conduct semi-rational/rational design (substrate channel remodeling, active pocket engineering, flexible regulation, N-terminal/C-terminal and surface charge optimization), reducing the number of evolution rounds and improving the hit rate of modification;

Form a closed loop of "computational prediction - experimental verification - feedback iteration" with the experimental team to consolidate the general rules library for enzyme modification.