Pharma Mar, S.a.

Fernando De La Calle

Ignacio Manzanares

Carmen Cuevas

Pilar Gallego

Marta Perez

Maria Zarzuelo

Jose Luis Chicharro

Carolina Fernandez

Ana Velasco Iglesias

Tomás Aparicio Pérez

Carmen Schleissner Sánchez

Paloma Acebo Páis

Pilar Rodríguez Ramos

Fernando Reyes Benítez

Rubén Henrìquez Peláez

A gene cluster is disclosed having open reading frames which encode polypeptides sufficient to direct the synthesis of a safracin molecule. In addition, the present disclosure is directed to a nucleic acid sequence, suitably an isolated nucleic acid sequence, which includes or comprises at least SEQ ID NO:1, variants or portions thereof, or at least one of the sacA, sacB, sacC, sacC, sacD, sacE, sacF, sacG, sacH, sacH, saI, sacJ, orf1, orf2, orf3 or orf4 genes, including variants or portions.

Gene cluster involved in safracin biosynthesis and its uses for genetic engineering

Methods are provided for preparing a compound with a fused ring structure of formula (XIV) which comprises one or more reactions starting from a 21-cyano compound of formula (XVI) where typically: Ris an amidomethylene group or an acyloxymethylene group; Rand Rare independently chosen from &#x2014;H, &#x2014;OH or &#x2014;OCOCHOH, or Rand Rare both keto and the ring A is a p-benzoquinone ring; Rand Rare both &#x2014;H ozone is &#x2014;H and the other is &#x2014;OH, &#x2014;OCHor &#x2014;OCHCH, or Rand Rtogether form a keto group; and Rand Rare independently chosen from &#x2014;H or &#x2014;OH, or Rand Rare both keto and the ring A is a p-benzoquinone ring. In modified starting materials, the 21-cyano group can be replaced by other groups introduced using nucleophilic reagents.

Hemisynthetic method and new compounds

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Madrid, Spain

Fernando De La Calle