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Ultrahigh Throughput Microscale Mass Spectrometry for Pharmaceutical Prenylation Enzyme Engineering

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R41GM143989-01
Agency Tracking Number: R41GM143989
Amount: $253,795.00
Phase: Phase I
Program: STTR
Solicitation Topic Code: 400
Solicitation Number: PA20-265
Solicitation Year: 2020
Award Year: 2021
Award Start Date (Proposal Award Date): 2021-09-25
Award End Date (Contract End Date): 2022-03-24
Small Business Information
Daly City, CA 94015-4714
United States
DUNS: 117062937
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: Yes
Principal Investigator
 Robin Prince
 (617) 620-2999
Business Contact
Phone: (512) 897-0737
Research Institution
SAN FRANCISCO, CA 94143-2510
United States

 Nonprofit College or University

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.Narrative
Biocatalyst such as prenylation enzyme is a key element in the discovery, production, and pharmaceutical application
of natural products; however, access to sufficiently functional biocatalysts often requires dedicated discovery and
reengineering before they can be used. The goal of this project will be to develop a platform for high throughput
engineering aromatic prenyltransferase, NphB, which has direct applications to produce novel pharmaceutical active
compounds from the phenylpropanoids, cannabinoids, and aromatic chemical families. Furthermore, the platform
developed during this project is highly extendable to other drug discovery or pharmaceutical discovery efforts.

* Information listed above is at the time of submission. *

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