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PMID: 9098068 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Minimal Streptomyces sp. strain C5 daunorubicin polyketide biosynthesis genes required for aklanonic acid biosynthesis.

Journal of bacteriology ·Vol. 179 ·No. 8 ·1997-04-00 ·Pages 2690-6

Rajgarhia VB, Strohl WR

Abstract

The structure of the Streptomyces sp. strain C5 daunorubicin type II polyketide synthase (PKS) gene region is different from that of other known type II PKS gene clusters. Directly downstream of the genes encoding ketoacylsynthase alpha and beta (KS alpha, KS beta) are two genes (dpsC, dpsD) encoding proteins of unproven function, both absent from other type II PKS gene clusters. Also in contrast to other type II PKS clusters, the gene encoding the acyl carrier protein (ACP), dpsG, is located about 6.8 kbp upstream of the genes encoding the daunorubicin KS alpha and KS beta. In this work, we demonstrate that the minimal genes required to produce aklanonic acid in heterologous hosts are dpsG (ACP), dauI (regulatory activator), dpsA (KS alpha), dpsB (KS beta), dpsF (aromatase), dpsE (polyketide reductase), and dauG (putative deoxyaklanonic acid oxygenase). The two unusual open reading frames, dpsC (KASIII homolog lacking a known active site) and dpsD (acyltransferase homolog), are not required to synthesize aklanonic acid. Additionally, replacement of dpsD or dpsCD in Streptomyces sp. strain C5 with a neomycin resistance gene (aphI) results in mutant strains that still produced anthracyclines.

MeSH Terms
Aclarubicin/biosynthesis Acyltransferases/genetics,physiology Anthraquinones/metabolism Chromosomes, Bacterial Daunorubicin/biosynthesis Genes, Bacterial/genetics Models, Chemical Mutation Open Reading Frames/genetics Restriction Mapping Species Specificity Streptomyces/enzymology,genetics,metabolism
Chemicals
Anthraquinones Aclarubicin aklanonic acid Acyltransferases actinorhodin Daunorubicin
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Rajgarhia V B
Department of Microbiology, The Ohio State University, Columbus 43210, USA.
Strohl W R
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Article Info
Journal
Journal of bacteriology
Abbr.
J Bacteriol
ISSN
0021-9193
DOI
10.1128/jb.179.8.2690-2696.1997
Published
1997-04-00
Pages
2690-6
Language
English
Region
United States
NLM ID
2985120R
PMCID
PMC179019
Subset
IM
External Links
PubMed source DOI: 10.1128/jb.179.8.2690-2696.1997 PMC Full Text View journal details
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