NRPS-PKS gene cluster and its manipulation and utility

摘要

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.