Hyaluronic acid micro factory : A bacterium produces low molecular weight hyaluronic acid
Engineering strain : Bacillus subtilis
Genetic origin : Streptococcus equi and Leech


The production of hyaluronic acid has been changed from traditional animal tissue formulation to microbial fermentation. However, there is no report that tissue cells or microorganisms can di-rectly produce low molecular weight hyaluronic acid. In order to prepare low molecular weight hyaluronic acid, physical and chemical methods are needed. However, there are many drawbacks in physical and chemical methods, such as poor product stability, low efficiency, complex reac-tion conditions and possible environmental pollution.

This year our project constructed a recombinant strain Bacillus subtilis 168E which could directly produce different molecular weight hyaluronic acid products by regulating the activities of LHAase. Bacillus subtilis 168 was selected as the best chassis. The HasA gene and identified pre-cursor genes (tuaD , gtaB , gluM , glmM and glmS) was transferred into Bacillus subtilis. Since hyaluronic acid of high molecular weight was produced at this time, we transferred the LHAase gene into Bacillus subtilis 168 which is from leech resources coding hyaluronidase. Therefore the hyaluronic acid could be enzymatic hydrolyzed to different molecular weight.

Our intended application is use low molecular weight hyaluronic acid to prepare microneedles and that hyaluronic acid can be dissolved and stuck in the skin under the action of body fluid when it is punctured into the human skin, microneedles allow the penetration of low molecular weight HA through to the dermal papillary cutis, which could not only play a cosmetic role. Be-cause hyaluronic acid is an endogenous substance of the human body and does not cause the in-flammatory reaction, therefore it is a new type of microneedle material and has a potential mar-ket.