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Updated: Sep 26, 2026

Functionalized Spirocyclic Heterocycle Synthesis and Cytotoxicity Assay
Published on: February 9, 2021
Studies on a second and third ring cyclization in anthracycline biosynthesis
Anne Hautala1, Sirke Torkkell, Kaj Räty
1Galilaeus Oy, P.O. Box 113, FIN-20781, Kaarina, Finland. anne.hautala@galilaeus.fi
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.
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