(6x) Engineering Multienzyme Systems for the Next Generation of Biomanufacturing

Research Interests:

    Rational design of nanoscale biochemical factories is highly appealing for the
next generation of biomanufacturing. Enzymes are the
primary building blocks to assemble such molecular factories. My research aims to
understand the reaction kinetics and system dynamics of multienzyme
systems, and to integrate the enzymes in a synthetic way to realize defined,
programmable and life-like functions in
vitro. Focusing on dynamic behaviors of a synthetic biological system will
provide new insights on non-steady or non-equilibrium states, and will
eventually lead to evolutionary developments in biocatalysis,
diagnostics, and adaptive biochemical devices.

    I participated in the rapid
development of biocatalysis in the past decade. My
doctoral research focused on the development of stimuli-responsive enzyme
catalysts and the application of enzymes in organic synthesis. Then I started
research on multienzyme catalysis in the last phase
of my doctoral study. As a postdoctoral researcher in the lab of Prof. Henry
Hess, I am mainly working towards the understanding of the activity
enhancements of enzyme cascades and the complex dynamics of enzymatic reaction
networks. I experimentally demonstrated that the microenvironment rather than
proximity channeling causes the activity enhancements of enzyme cascades on DNA
scaffolds. Later on, I discovered the smallest enzymatic reaction network which
can generate complex dynamics and Rayleigh-Bernard convective
patterns.

    My future work will focus on
the development and application of multienzyme
systems, and the construction of synthetic intelligent devices with autonomous
and adaptive behaviors. I plan to pursue the following research thrusts as a
faculty member: (1) Application of non-aqueous multienzyme
systems for the degradation of plastics and biosynthesis of fine chemicals; (2)
Process engineering of non-ribosomal peptide synthetases
for the sequential synthesis of non-ribosomal peptides; (3) Bottom-up assembly
of enzymatic reaction networks for intelligent devices based on self-regulating
biochemistry.

Teaching Interests:

    I genuinely enjoy teaching
and mentoring students. I have extensive experience as a teaching assistant in
four courses at both undergraduate and graduate levels at Tsinghua
University and Columbia University. I have mentored twelve students in nine
research projects and eight of them published their research in peer-reviewed
journals. Now most of these students have become productive researchers
pursuing Ph.D. degrees at institutions such as the Massachusetts Institute of
Technology, Stanford University, the University of Minnesota, the University of
Washington and Tsinghua University.

    As I obtained both my
bachelor's and doctoral degree in Chemical Engineering at Tsinghua
University, an ABET accredited program, I am comfortable to teach core courses such
as thermodynamics, transport processes, chemical reaction engineering, and
separation processes as well as specialized courses like biochemical engineering
and bioseparation processes. I am also eager to
develop a course, Nanoengineering in Biocatalysis,
to introduce the fundamentals and recent developments of biocatalysis
and the influence of nanotechnology on the field.

Selected Publications (28 total, 11
first author, 600+ citations):

1.   
Yifei Zhang, Stanislav Tsitkov, Henry
Hess. Complex dynamics in a
two-enzyme reaction network with substrate competition, Nature Catalysis 2018, 1, 276−281 (Featured on the cover).

2.   
Yifei Zhang, and Henry Hess. Toward rational design of
high-efficiency enzyme cascade. ACS Catalysis 2017, 7, 6018−6027.

3.   
Yifei Zhang, Qin Wang, Henry Hess. Increasing enzyme cascade
throughput by pH-engineering the microenvironment of individual enzymes. ACS
Catalysis 2017, 7, 2047−2051.

4.   
Yifei Zhang, Stanislav Tsitkov, Henry Hess. Proximity does not contribute to
activity enhancement in the glucose oxidase-horseradish
peroxidase cascade. Nature Communications 2016, 7, 13982.

5.   
Yifei Zhang, You Yong, Jun Ge, Zheng Liu. Lectin agglutinated multienzyme catalyst with enhanced substrate affinity and
activity. ACS Catalysis 2016, 6, 3789−3795.

6.   
Yifei Zhang, Jun Ge and Zheng
Liu. Enhanced activity of immobilized or chemically modified enzymes. ACS
Catalysis 2015, 5, 4503−4513.

7.    Yifei Zhang, Fengjiao Lyu, Jun Ge, Zheng
Liu. Ink-jet printing an optimal multi-enzyme system. Chemical Communications
2014, 50, 12919−12922.

External links:

1. Homepage at
https://sites.google.com/view/yifeizhang

2. Google
scholar at https://scholar.google.com/citations?user=sqc421QAAAAJ