# BIOSYNTHESIS OF ANTHRACYCLINE ANTIBIOTICS

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 1988 · $145,543

## Abstract

This proposal requests continuation of our study of the
biochemistry and genetics of anthracycline antibiotic biosynthesis
for a five year period.  During this time we will (i) isolate and
study the properties of the socalled " aromatic polyketide
synthases" and their structural genes, (ii) define the genetic and
biochemical organization of anthracycline antibiotic biosynthetic
pathways with special emphasis on their regulation at DNA, RNA
and protein levels, and (iii) explore the possibilities for expressing
Streptomyces genes in other actinomycetes and creating new
anthracycline antibiotics by genetic engineering.

The major project during this period will be a study of
tetracenomycin C, and antitumor antibiotic produced by
Streptomyces glaucescens.  We will complete the cloning of the
tcm genes then dissect the tcm gene cluster by standard
techniques individual tcm genes.  Their structures will be studied
by nucleotide sequencing, S1 mapping, and other methods to
locate the regulatory regions and transcriptional/translational
start/stop sites.  This information and the results of Northern
hybridizations will be used to identify the transcriptional units
within the tcm gene cluster.  The enzymes catalyzing the
formation of the aromatic polyketide intermediates of TcmC
biosythesis will be overproduced by inserting their genes in
suitable expression vectors to facilitate the study of their
physical and biochemical properties.  In this way we will establish
information about the regulation of TcmC biosynthesis at the
DNA, RNA and protein levels.

Subsidiary projects will involve cloning the genes for the
production of elloramycin, an analog of TcmC; using the tcm
genes as probes for genes governing related biochemical pathways
in Streptomyces; expressing the tcm genes in other
actinomycetes; and exploring the possibilities for the construction
of hybrid anthracyclines by genetic engineering.

## Key facts

- **NIH application ID:** 3172999
- **Project number:** 5R01CA035381-06
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **SAM.gov UEI:** LCLSJAGTNZQ7
- **Principal Investigator:** CHARLES R HUTCHINSON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $145,543
- **Award type:** 5
- **Project period:** 1986-09-01 → 1991-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3172999

## Citation

> US National Institutes of Health, RePORTER application 3172999, BIOSYNTHESIS OF ANTHRACYCLINE ANTIBIOTICS (5R01CA035381-06). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3172999. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*