Award Abstract # 2204014
Synthetic Biology Approaches to Selective Amino Acid Modification and Incorporation

NSF Org: CHE
Division Of Chemistry
Recipient: REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE
Initial Amendment Date: August 29, 2022
Latest Amendment Date: August 29, 2022
Award Number: 2204014
Award Instrument: Standard Grant
Program Manager: Pui Ho
puiho@nsf.gov
 (703)292-0000
CHE
 Division Of Chemistry
MPS
 Directorate for Mathematical and Physical Sciences
Start Date: September 1, 2022
End Date: August 31, 2025 (Estimated)
Total Intended Award Amount: $528,000.00
Total Awarded Amount to Date: $528,000.00
Funds Obligated to Date: FY 2022 = $528,000.00
History of Investigator:
  • Michelle Chang (Principal Investigator)
    mcchang@berkeley.edu
Recipient Sponsored Research Office: University of California-Berkeley
1608 4TH ST STE 201
BERKELEY
CA  US  94710-1749
(510)643-3891
Sponsor Congressional District: 12
Primary Place of Performance: University of California-Berkeley
124 Lewis Hall
Berkeley
CA  US  94720-1460
Primary Place of Performance
Congressional District:
12
Unique Entity Identifier (UEI): GS3YEVSS12N6
Parent UEI:
NSF Program(s): Chemistry of Life Processes
Primary Program Source: 01002223DB NSF RESEARCH & RELATED ACTIVIT
Program Reference Code(s): 8038
Program Element Code(s): 688300
Award Agency Code: 4900
Fund Agency Code: 4900
Assistance Listing Number(s): 47.049

ABSTRACT

With the support of the Chemistry of Life Processes Program in the Chemistry Division, Professor Michelle Chang from the University of California, Berkeley will develop methods for the incorporation of non-canonical amino acids into proteins. Although proteins carry out a broad range of functions in the cell, they are ostensibly made up a limited set of 20 standard amino acids that represent a limited range of chemical functionality compared to what can be utilized by chemists. However, nature also provides many genetically-encoded pathways to produce novel amino acids with unusual functionality that are typically not incorporated into proteins. The proposed research will utilize a pathway discovered by the Chang group that produces amino acids bearing halo, terminal alkene, and terminal alkyne functionality and will develop methods for the incorporation of these amino acids into proteins. The Chang group will further focus on a new bioinformatic strategy to identify novel pathways for biosynthesis of non-standard amino acids by using new marker enzymes known to cluster with genes involved in the biosynthesis of the amino acid itself. Further exploration of these new gene clusters can shed light on the role of non-standard amino acids in metabolism while also providing a tool to expand the diversity of proteins that can be made. This pursuit will allow graduate students and postdoctoral fellows to be broadly trained at the interface of chemistry and biology. This project will also be integrated with an outreach program to introduce K-5 students to concepts at the interface of chemistry and biology, with a focus on green chemistry.

This research project focuses on the development of a bioinformatic strategy to identify novel pathways for biosynthesis of non-standard amino acids. Professor Michelle Chang and her research team will use a resistance marker to identify a wide range of gene clusters that seemingly encode the biosynthesis of new amino acids and related natural products. These gene clusters and their products will be characterized. The new knowledge will be used to expand the scope of non-standard amino acids that can be produced enzymatically. Such an approach promises to open up the possibility of introducing malleable new chemical functionalities, including alkene and alkyne groups, into targeted positions in tailored proteins. The study of the resistance enzymes will provide insight in the recognition of non-standard amino acids and will be used to design tools for residue-selective incorporation of the non-proteinogenic amino acids.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

Please report errors in award information by writing to: awardsearch@nsf.gov.

Print this page

Back to Top of page