Home
Resources
Publications
Involvement of a Chromomycin ABC Transporter System in Secretion of a Deacetylated Precursor During Chromomycin Biosynthesis

Involvement of a Chromomycin ABC Transporter System in Secretion of a Deacetylated Precursor During Chromomycin Biosynthesis

Nuria Menéndez, Alfredo F Braña, José A Salas, Carmen Méndez

Microbiology. 2007 Sep;153(Pt 9):3061-3070.

PMID: 17768249

Abstract:

Chromomycin A(3) is an antitumour antibiotic that acts by inhibiting transcription and replication of DNA. The producer micro-organism Streptomyces griseus subsp. griseus is highly resistant to chromomycin A(3) and to the structurally related compound mithramycin upon induction with chromomycin A(3). The biosynthetic gene cluster of chromomycin contains three genes involved in self-resistance to chromomycin in S. griseus: cmrA and cmrB encode a type I ATP-binding cassette (ABC) transporter, and cmrX encodes a UvrA-like protein of ABC excision nuclease systems. These genes are linked in the chromosome, together with a gene encoding a transcriptional repressor (cmmRII). Involvement of these genes in chromomycin resistance was determined through gene inactivation, and heterologous expression in Streptomyces albus. Inactivation of cmrX produced a chromomycin-sensitive low-producer strain, while inactivation of cmmRII generated a high-chromomycin-producer strain, which was resistant to chromomycin, and also to mithramycin. Expression of either cmrA and cmrB, or cmrX, in S. albus generated strains with low chromomycin resistance; it was therefore necessary to co-express the three genes to achieve high levels of resistance. However, the CmrAB ABC transporter conferred a high level of resistance to the biosynthesis intermediate 4A,4E-O-dideacetyl-chromomycin A(3). A model is proposed for the biosynthesis of, and self-resistance to, chromomycin A(3) in S. griseus subsp. griseus.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP7059247	Chromomycin A3 from Streptomyces griseus		7059-24-7	Price

As a specialist in analytical chemical Products, Alfa Chemistry offers consumers a wealth of raw materials and a full range of technologies and services.

QUICK LINKS

HEADQUARTERS

Tel:

Fax:

Email: