Project Summary
Biocatalyst can be key tools in the synthesis of natural product-based pharmaceuticals and as powerful components
of the pharmaceutical chemist’s drug modification kit. For example, the aromatic prenyltransferase NphB has utility in
the synthesis of common prenylated compounds or derived backbones include cannabinoids, alpha acids, beta acids,
phenylpropanoids, naphterpins, and marinones. The same enzyme also has utility as a general tool for compound
functionalization. Our partner, BioMediCan has developed a whole cell biocatalysis platform based on this enzyme for
production of natural and nonnatural rare cannabinoids. However, for all the attractive qualities and uses of enzyme-
based or whole-cell biocatalysis, NphB as well as many other enzymes have not evolved with the characteristics
required for industrial or pharmaceutical goals. These limitations arise because of the limitations of conventional
analytical methods and the narrow detection capabilities of the current suite of ultrahigh-throughput microfluidic
techniques. To develop novel high efficient platform and to improve the NphB biocatalyst, Fluid Discovery will engineer
a microfluidic based biocatalysis sample preparation system with capacities of high throughput sample processing
and low cost and enable its seamless coupling with matrix-assisted laser desorption/ionization (MALDI) mass
spectrometry for high sensitivity and general applicability. This method, called μMALDI-TOF, will not only allow Fluid
Discovery and BioMediCan to take the first steps towards becoming a key provider of novel compounds and enzymatic
tools, but also provide a quantum leap in biocatalyst discovery and engineering through a highly scalable and universal
screening platform. Our Phase I goal is to establish and demonstrate the capacity of this platform on engineering
NphB in whole cell biocatalysis. In Phase II, we will continue our work via engineering NphB for improving and
expanding the current whole-cell biocatalyst platform and initiate contracted service to early access synthetic biology
companies. Ultimately, we plan to leverage the generality of our product for applications in the generation of
biocatalysts for either green chemistry drug production or as tools for the molecular diversification that underlies lead
compound modification and optimization.
