# Biosynthesis of Marine Polyketide Antibiotics

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $348,750

## Abstract

Project Summary / Abstract 
 
The  emergence  of  antibiotic  resistance  has  created  a  global  dilemma  for  the  need  to  discover 
new antibacterial lead agents. Realizing this critical need for new antibacterial agents with new 
structure types and targets, we focus here on the biosynthetic interrogation and development of 
structurally  distinct  marine  bacterial  natural  products.  An  underlying  theme  associated  with 
many marine microbial antibiotics involves the use of aromatic polyketide frameworks that have 
undergone  extensive  oxidative  tailoring  reactions  catalyzed  by  halogenase  and  oxygenase 
biosynthetic  enzymes.  In  this  application,  we  propose  a  multidisciplinary  project  involving 
heterologous  biosynthesis,  mechanistic  enzymology,  atomic  resolution  protein  X-­ray 
crystallography, chemoenzymatic synthesis, and genetic engineering to understand and control 
the molecular basis of polyketide diversification in a series of marine bacterial compounds with 
promising  antimicrobial  properties.  To  accomplish  the  broad  goals  outlined  in  this  application, 
we propose four specific aims. First, we plan to functionally and structurally characterize diverse 
meroterpenoid  V-­dependent  chloroperoxidases  and  their  catalytic  properties  in  promoting 
antimicrobial  chemical  diversity.  Second,  we  will  discover,  characterize,  and  engineer 
biosynthetic  pathways  for  structural  diversification  of  halogenated  pyrrole  containing  bioactive 
natural  products.  Third,  we  aim  to  functionally  characterize  the  unprecedented  biosynthesis  of 
thiotetronic  acid  polyketide  antibiotics  and  apply  new  biosynthetic  reactions  to  extend  the 
synthesis  and  bioengineering  of  novel  molecules.  And  fourth,  we  will  interrogate  the 
antimicrobial  activity  and  mechanism  of  new  meroterpenoid,  bipyrrole,  and  thiotetronate 
compounds.

## Key facts

- **NIH application ID:** 9834820
- **Project number:** 5R01AI047818-19
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** BRADLEY S MOORE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $348,750
- **Award type:** 5
- **Project period:** 2000-08-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9834820

## Citation

> US National Institutes of Health, RePORTER application 9834820, Biosynthesis of Marine Polyketide Antibiotics (5R01AI047818-19). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9834820. Licensed CC0.

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