Synthetic Biology Group

The research of Synthetic Biology Group is focused on increasing the production of secondary metabolites from microbial producers by synthetic biology. Avermectin produced by Streptomyces avermitilis is used as a case study. The avermectin B1a production was successfully improved in an industrial overproducer by the following parts:

1) Novel mutagenesis methods

Mutant libraries of avermectins-producer Streptomyces avermitilis were constructed by different mutagenesis strategies. Traditional physical and chemical mutagenesis methods, such as UV, microwave, 5 - fluorouracil, NTG, were used to improve avermectin production. And for the first time, the magnetic-gravity environment (high magneto-gravitational environ- ment, HMGE) was used to increase the strain diversity. The results showed for the first time that microgravity environment could introduce larger phenotype distribution and diversity than UV and NTG.

2) Identification of avermectin overproducer in a high-throughput manner

A high-throughput screening strategy was developed in a 96-deep-well microplate format. UV absorbance at 245 nm was used to monitor avermectin production. A good correlation between fermentation results in both deep-well microplates and conventional Erlenmeyer flasks was observed. With this protocol, the production of avermectins was determined in less than 10 min for a full plate without compromising accuracy. Thus, the development of this protocol is expected to accelerate the selection of superior avermectin-producing strains.

3) Medium optimization for the production of avermectin B1a using response surface methodology

Response surface methodology was employed to optimize the composition of medium for the production of avermectin B1a by Streptomyces avermitilis in shaker flask cultivation. Corn starch and yeast extract were found to have significant effects on avermectin B1a production by the Plackett–Burman design. The steepest ascent method was used to access the optimal region of the medium composition, followed by an application of response surface.

4) Increasing yields of avermectin by synthetic biology approaches

We focused on the design and synthesis of biological chassis, parts, device and modules from the microbial diversity on the planet to reconstruct and optimize their dynamical process, as well as predict favorable effective overproduction of avermectin B1a. Evolutionary in silico analysis has a particular role here: create and observe efficient microbial evolution in ways not previously possible. We did a computational study on the de novo biosynthesis of avermectin B1a and followed by a 4M strategy.

Selected Publications