<P>Combinatorial biosynthesis of 5/5/6 type polycyclic tetramate macrolactams (PoTeMs) was achieved in an engineered ikarugamycin (5/6/5 type) producer by introducing a set of 5/5/6 type PoTeM biosynthetic genes from <I>Streptomyces griseus</I>. This study supports the idea that PoTeMs share a common polyene tetramate precursor generated by the hybrid polyketide synthase/nonribosomal peptide synthetase enzymes. The X-ray crystal structure of pactamide G (<B>7</B>) sets an example for resolving the absolute configuration of 5/5/6 type PoTeMs.</P><BR>[FIG OMISSION]</BR>