Katharine Watts
California Polytechnic State University-San Luis Obispo, CA·Biochemistry
Many bacteria are now resistant to the antibiotics we rely on, so new antibiotic molecules are needed. Many natural antibiotics are built inside microbes in a modular way, like snapping together building blocks.
- Fields
Biochemistry
Microbiology & Immunology
Chemistry
- Topics
natural products
polyketides
antibiotic biosynthesis
- Grants
- 1 known grant, through Mar 2027
What they work on
- Identify the role of individual genes in TLN-05220 biosynthesis by making gene knockouts in the wild-type bacterium that naturally produces this Echinosporamicin-type antibiotic.
- Predict substrate binding sites and catalytic residues in the enzymes that attach amino acids to the polyketide scaffold, using homology modeling, which builds protein structures from related known proteins.
- Express and characterize individual amino acid-incorporating enzymes to determine how they attach amino acids to natural product structures without NRPS assembly-line machinery.
- Clone the minimal set of genes needed to make TLN-05220 and express them in a heterologous host, a separate, easier-to-grow organism, to reconstitute production.
More about the research
If scientists understood the rules for how each block is attached, they could shuffle the blocks to design new antibiotics. This project studies one unusual kind of connection: how amino acids, the building blocks of proteins, get attached to polyketides. Polyketides are a large family of natural products assembled from simple carbon units. Here the amino acids are added without using NRPS (nonribosomal peptide synthetase) machinery, the assembly-line enzymes that usually do this job.
Why it matters
Antibiotic resistance makes infections such as MRSA and VRE harder to treat. Design rules for how microbial enzymes attach amino acids to polyketide scaffolds could let researchers mix and match biosynthetic building blocks to produce new, non-natural antibiotic candidates. Moving the TLN-05220 pathway into an easier host may also make this compound and its variants more practical to produce and study.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Madan Kharel
University of Maryland Eastern Shore, MD·Biochemistry
Identify the biosynthetic building blocks of manzamine A's beta-carboline unit and five-ring core using isotope incorporation experiments in Micromonospora sp. M42.
Robert Clubb
University of California-Los Angeles, CA·Biochemistry
Determine how the C. diphtheriae surface receptor HbpA captures human hemoglobin, and test whether it works with other heme-binding receptors to distort hemoglobin and trigger heme release.
Lilly Immergluck
Morehouse School of Medicine, GA·Public Health & Epidemiology
Apply association mining to antibiotic resistance phenotypes of community-onset Staphylococcus aureus from children to identify which resistance patterns co-occur and how multidrug-resistant profiles have changed over two decades.
The school
California Polytechnic State University-San Luis Obispo: 7 labs on PI Pages, $38M a year on research.
More about California Polytechnic State University-San Luis Obispo
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