The antimalarial polyketide plakortin is found in high concentrations in the extracts of sponges of the genus Plakortis (order Homosclerophorida, family Plakinidae). Numerous similar polyketides containing one endoperoxide ring can be found in these and other sponges, as well. It was intended to find the polyketide synthase (PKS) genes for plakortin in the collective genomic DNA (metagenome) of Plakortis simplex and its bacterial symbionts, the latter being supposed to be the true producers of plakortin. The PCR screening with oligonucleotides targeting conserved aminoacid motifs of multifunctional, modular PKSs (referred to as type I PKSs) yielded in the discovery of two interesting PKS amplicons. Using these amplicons as probes, two PKS gene clusters were isolated from a metagenomic library of ~245,000 fosmids and sequenced completely. Since these two clusters are very similar to a newly found PKS from a ubiquitous symbiont of many sponges they are unlikely to be the gene clusters for plakortin, but their function is still unknown. Other gene targets, more specific to plakortin were used, but without success: e.g., a gene for a putative endoperoxide forming oxygenase, the gene for a crotonyl-CoA reductase that is frequently present in clusters for polyketides that incorporate butyrate units derived from ethylmalonyl-CoA, and acyltransferase genes having substrate specificity to ethylmalonyl-CoA. Currently, with the 454-based deep sequencing of ~25,000 PKS amplicons a new approach is ongoing to find the gene cluster for plakortin as a pre-condition of its heterologous sustainable production by fermentation.

Biosynthesis of Plakortin / Thomas, Hochmuth; DELLA SALA, Gerardo; Teta, Roberta; Costantino, Valeria; Ernesto, Fattorusso; Mangoni, Alfonso. - STAMPA. - (2011), pp. Nea4-Nea4. (Intervento presentato al convegno NatPharma: Nature Aided Drug Discovery Meeting tenutosi a Napoli nel 5-9 June 2011).

Biosynthesis of Plakortin

DELLA SALA, GERARDO;TETA, ROBERTA;COSTANTINO, VALERIA;MANGONI, ALFONSO
2011

Abstract

The antimalarial polyketide plakortin is found in high concentrations in the extracts of sponges of the genus Plakortis (order Homosclerophorida, family Plakinidae). Numerous similar polyketides containing one endoperoxide ring can be found in these and other sponges, as well. It was intended to find the polyketide synthase (PKS) genes for plakortin in the collective genomic DNA (metagenome) of Plakortis simplex and its bacterial symbionts, the latter being supposed to be the true producers of plakortin. The PCR screening with oligonucleotides targeting conserved aminoacid motifs of multifunctional, modular PKSs (referred to as type I PKSs) yielded in the discovery of two interesting PKS amplicons. Using these amplicons as probes, two PKS gene clusters were isolated from a metagenomic library of ~245,000 fosmids and sequenced completely. Since these two clusters are very similar to a newly found PKS from a ubiquitous symbiont of many sponges they are unlikely to be the gene clusters for plakortin, but their function is still unknown. Other gene targets, more specific to plakortin were used, but without success: e.g., a gene for a putative endoperoxide forming oxygenase, the gene for a crotonyl-CoA reductase that is frequently present in clusters for polyketides that incorporate butyrate units derived from ethylmalonyl-CoA, and acyltransferase genes having substrate specificity to ethylmalonyl-CoA. Currently, with the 454-based deep sequencing of ~25,000 PKS amplicons a new approach is ongoing to find the gene cluster for plakortin as a pre-condition of its heterologous sustainable production by fermentation.
2011
Biosynthesis of Plakortin / Thomas, Hochmuth; DELLA SALA, Gerardo; Teta, Roberta; Costantino, Valeria; Ernesto, Fattorusso; Mangoni, Alfonso. - STAMPA. - (2011), pp. Nea4-Nea4. (Intervento presentato al convegno NatPharma: Nature Aided Drug Discovery Meeting tenutosi a Napoli nel 5-9 June 2011).
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/520240
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