Cloning, sequencing, and heterologous expression of the elmGHIJ genes involved in the biosynthesis of the polyketide antibiotic elloramycin from Streptomyces olivaceus Tu2353

Citation
Er. Rafanan et al., Cloning, sequencing, and heterologous expression of the elmGHIJ genes involved in the biosynthesis of the polyketide antibiotic elloramycin from Streptomyces olivaceus Tu2353, J NAT PROD, 64(4), 2001, pp. 444-449
Citations number
38
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Agricultural Chemistry","Pharmacology & Toxicology
Journal title
JOURNAL OF NATURAL PRODUCTS
ISSN journal
0163-3864 → ACNP
Volume
64
Issue
4
Year of publication
2001
Pages
444 - 449
Database
ISI
SICI code
0163-3864(200104)64:4<444:CSAHEO>2.0.ZU;2-Z
Abstract
Elloramycin A (1) belongs to a small family of naphthacenequinones characte rized by a unique highly hydroxylated cyclohexenone moiety. A cosmid clone 16F4, harboring genes for the production of 1 from Streptomyces olivaceus T u2353, has been previously isolated. DNA sequence analysis of a 3.2-kb frag ment from 16F4 revealed four open reading frames-the elmGHIJ genes. Heterol ogous expressions of the elmGHI genes in either Escherichia coli or Strepto myces lividans, followed by biochemical characterizations of the ElmGHI pro teins, established ElmG as tetracenomycin B2 oxygenase, ElmH as tetracenomy cin Fl monooxygenase, and ElmI as tetracenomycin F2 cyclase. These results provide direct biochemical evidence for the hypothesis that the biosynthesi s of 1 in S. olivaceus parallels that of tetracenomycin C (2) in Streptomyc es glaucescens and support the notion that the biosynthesis of the highly h ydroxylated cyclohexenone moiety in other polyketides most likely follows t he same paradigm as the tetracenomycin B2 or A2 oxygenase.