Targeted disruption ofStreptomyces globisporus lndF andlndL cyclase genes involved in landomycin E biosynthesis

Streptomyces globisporus strains with knockouts inlndF andlndL genes, previously identified as possibly encoding cyclases governing cyclization of the nascent oligoketide (‘polyketide’) chain during the biosynthesis of the antitumor angucycline landomycin E, were prepared. On combining the results of sequence analysis and HPLC of extracts from mutant strains,lndL was suggested to control the first cyclization-aromatization event andlndF to be responsible for the 3rd–4th ring formation.