Sintef Tto As

Sinvent As

Per Bruheim

Sergey Zotchev

Trond Erling Ellingsen

Geir Klinkenberg

Kristin Fløgstad Degnes

Hanne Jørgensen

Havard Sletta

Håvard Sletta

Espen Fjærvik

Espen Fjaervik

Kristin Flogstad Degnes

Hanne Jorgensen

A nucleic acid molecule comprises a nucleotide sequence: as shown in SEQ ID No. 1, which is the complement of SEQ ID No. 1, which is degenerate with SEQ ID No. 1, or which has at least 85% sequence identity with SEQ ID No. 1, or which is a part of such a sequence. The nucleic acid molecule encodes or is a complementary to a nucleic acid molecule encoding one or more polypeptides, or comprises or is complementary to a nucleic acid molecule comprising one or more genetic elements, having functional activity in the synthesis of a polyketide-based or macrolactam molecule. The nucleic acid molecule may be used to prepare a modified BE-14106 biosynthetic gene cluster for the preparation of a modified BE-14106 molecule.

NRPS-PKS gene cluster and its manipulation and utility

The present invention provides a nucleic acid molecule comprising: (a) a nucleotide sequence as shown in SEQ ID No. 1; or (b) a nucleotide sequence which is the complement of SEQ ID No. 1; or (c) a nucleotide sequence which is degenerate with SEQ ID No. 1; or (d) a nucleotide sequence having at least 85% sequence identity (preferably at least 87%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity) with SEQ ID No. 1; or (e) a part of any one of (a) to (d), wherein said nucleic acid molecule encodes or is a complementary to a nucleic acid molecule encoding one or more polypeptides, or comprises or is complementary to a nucleic acid molecule comprising one or more genetic elements, having functional activity in the synthesis of a polyketide-based or macrolactam molecule. Particularly the invention contemplates the modification of the nucleic acid of the invention, encoding the biosynthetic machinery for the synthesis of the polyketide macrolactam BE-14106, including expressing in a microorganism the modified nucleic acid molecule. In certain aspects the modification includes introducing, mutating, deleting, replacing or inactivating a sequence encoding one or more activities or proteins encoded by said nucleic acid molecule. Other aspects of the invention include a microorganism containing the modified and unmodified nucleic acid and recovering the polyketide-based or macrolactam molecule from said microorganism.

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Trondheim, Norway

Per Bruheim