Genome mining of Streptomyces sp. LZ35

Yuemao Shen

Key Laboratory of Chemical Biology (Ministry of Education) School of Pharmaceutical Sciences, Shandong University, No. 44 West Wenhua Road, Jinan, Shandong 250012, China

With the advantage of whole-genome sequencing, actinomycetes, particularly Streptomyces spp., have been brought back into the spotlight because compared to other bacteria, they have relatively large genomes and possess more potential biosynthetic gene clusters. Since mining of bacteria with large genome has emerged as a major priority for discovery of natural products, several strategies have been developed to unveil novel metabolites that were overlooked under standard laboratory conditions. With overexpression of positive transcriptional factors and successive disruptions of the biosynthesis of the major metabolites, we isolated ten types of secondary metabolites, i.e. geldanamycins, cuevaenes, hygrocins, 16,17-dihydroxycyclooctatin, echosides, galbonolides, nigericins, elaiophylins, azalomycins and ortho-alkyl cinnamoyl lipothreonines from a geldanamycin high-yield marine Streptomyces sp. strain LZ35 from the intertidal soil collected at Jimei, Xiamen, P. R. China. Additionally, we characterized the biosynthesis of cuevaenes, hygrocins, echosides and galbonolides by bioinformatics analysis of gene clusters, genetic manipulations and/or in vitro reconstitutions.