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