Restricted Research - Award List, Note/Discussion Page

Fiscal Year: 2021

250  University of North Texas  (84546)

Principal Investigator: Skellam,Elizabeth Julia

Total Amount of Contract, Award, or Gift (Annual before 2011): $ 309,779

Exceeds $250,000 (Is it flagged?): Yes

Start and End Dates: - 2/29/24

Restricted Research: YES

Academic Discipline: Chemistry

Department, Center, School, or Institute: College of Science

Title of Contract, Award, or Gift: Developing a Biomanufacturing Platform for the Site-Selective Functionalization and Structural Diversification of Cytochalasan-Based Carbon Skeletons

Name of Granting or Contracting Agency/Entity: National Science Foundation

Program Title: N/A
CFDA Linked: Engineering Grants


1.1.1 (SAM); IBC Protocol #2021-04; Cytochalasans are phytotoxic, cytotoxic, and actin binding natural products produced by fungi with over 400 variants described. Despite their potential uses as agrochemicals, pharmaceuticals and cell imaging tools, only eight cytochalasans are commercially available (<$320/mg). The overall goal is to develop enabling technology for the biomanufacture of rationally designed molecules by meeting the following aims: 1) Elucidating the function of tailoring enzymes from various systems in vivo by utilizing genome mining to identify cytochalasan producers; characterizing producers chemically; inducing production by over-expression of the pathway specific transcriptional regulator; confirming the function and scope of tailoring enzymes by gene knock out and/or heterologous expression; 2) In vitro investigations to determine which tailoring enzymes can be developed as biocatalysts; assay development to determine suitability and scalability in biomanufacturing; enzyme engineering to expand the efficiency of individual enzymes; 3) Use synthetic biology and metabolic engineering tools to generate a clean biotransformation host resistant to cytochalasans for the large scale functionalization of externally added cytochalasan core motifs; investigate co-cultivation of engineered strains as a method for rapid structural diversification; 4) Biological testing of all molecules generated in a range of assays to understand structure activity relationships; 5) Inclusion of undergraduate and underrepresented students in interdisciplinary science, technology and engineering research with a long-term focus on commercial applications.

Discussion: No discussion notes


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