title: Studies on a second and third ring cyclization in anthracycline biosynthesis.
abstract: This paper focuses on study of second and third ring cyclization in anthracycline biosynthesis by a heterologous gene expression. Firstly, anthracycline non-producing Streptomyces peucetius mutant, D2 was heterologously complemented to produce daunomycins with plasmids pSgs44 and pSYE66, which contain putative cyclase genes of S. galilaeus and S. nogalater, respectively. A point mutation in the cyclase gene dpsY of D2 has changed glycine to serine resulting inactivation of the enzyme. Secondly, the putative cyclase gene snoaM from S. nogalater, was expressed in a gene cassette in S. lividans TK24 and S. coelicolor CH999 to study the influence of the cyclase gene on auramycinone production and the impact of endogenous genes on production profiles. The results obtained confirms that a cyclase closing the second and third ring of a polyketide is essential in anthracycline biosynthesis.
authors.affiliation: Galilaeus Oy, P.O. Box 113, FIN-20781, Kaarina, Finland. anne.hautala@galilaeus.fi
authors.forename: Anne
authors.initials: A
authors.lastname: Hautala
authors.forename: Sirke
authors.initials: S
authors.lastname: Torkkell
authors.forename: Kaj
authors.initials: K
authors.lastname: Räty
authors.forename: Tero
authors.initials: T
authors.lastname: Kunnari
authors.forename: Jaana
authors.initials: J
authors.lastname: Kantola
authors.forename: Pekka
authors.initials: P
authors.lastname: Mantsälä
authors.forename: Juha
authors.initials: J
authors.lastname: Hakala
authors.forename: Kristiina
authors.initials: K
authors.lastname: Ylihonko
mesh_terms: D018943:Anthracyclines / Q000378:metabolism*; D000903:Antibiotics, Antineoplastic / Q000378:metabolism*; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D003500:Cyclization; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics; D005798:Genes, Bacterial; D005816:Genetic Complementation Test; D016254:Mutagenesis, Insertional; D019906:Nuclear Magnetic Resonance, Biomolecular; D016133:Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics; D013302:Streptomyces / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*
chemical_list: D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic; D001426:Bacterial Proteins; D004269:DNA, Bacterial; C112173:DpsY protein, Streptomyces peucetius; D011994:Recombinant Proteins