Genome And Functional Gene Cluster Research For Marine Streptomyces Griseoaurantiacus M045

Specific environmental conditions can stimulate marine microorganisms to produce novel metabolites, and marine streptomycetes are important resources of bioactive compounds. Streptomyces griseoaurantiacus M045 isolated from sediment from Jiaozhou Bay in China produces manumycin A and chinikomycins antibiotics. Chinikomycins are the first discovered truly natural manumycin antibiotics with a para orientation of the side chains (p-aminobenzoic acid core component, pABA). Chinikomycins show moderate antitumor activity and inhibition of plant pathogenic fungi. Herein we present a draft genome sequence of S. griseoaurantiacus M045; it is the first sequenced streptomycete derived from the marine environment.The nucleotide sequence was determined using a 454 GS FLX sequencer. A total of 607,480 reads including up to 276,865,258 bp were obtained, which represented a 36-fold coverage of the genome. Assembly was performed using the GS de novo Assembler Software; it produced 60 contigs with a total size of 7,709,283 bp. In addition,570-fold coverage of pair-end sequences (2×120 bp) produced by Illumina Solexa technology was mapped to the genome sequence to promote sequence quality and fill in gaps. Finally, we obtained the S. griseoaurantiacus M045 draft genome of 7,712,377 bp distributed in 46 contigs with a GC content of 72.73%.Putative protein-coding sequences were predicted using Glimmer and GeneMark software. Functional annotation was based on the BLASTP with KEGG and NR databases. tRNA genes were directly predicted with tRNAscan-SE v1.23. The signal peptide cleavage sites, transmembrane topologies, and lipoproteins were predicted using SignalP3.0 with hidden Markov models, ConPredⅡ, and LipoP1.0, respectively. Genomic islands were predicted on the IslandViewer web service using the IslandPath-DIMOB and SIGI-HMM methods.The draft genome consists of one linear chromosome with 6 rRNA operons,65 tRNA genes, and 6839 protein-coding genes (CDSs). Among the CDSs,4416 proteins could be assigned to COG families. Biological functions could be assigned to 4966 (72.6%) of the predicted proteins, whereas 1259 CDSs (18.4%) are homologous to conserved proteins of unknown function in other organisms. The remaining 614 hypothetical proteins (9%) have no match to any known proteins in the databases. At least 660 multigene (paralog) families containing 2693 predicted proteins were identified. Two-component regulatory systems, which detect and respond to changes in the marine environment, are widely distributed on the chromosome.As for the subcellular localization of the proteins,234 proteins were identified as secreted proteins,1352 proteins as transmembrane proteins, and 106 proteins as lipoproteins. In addition,18 genomic islands occur in the genome; the genomic islands link secondary metabolism to functional and environmental adaptation in marine S. griseoaurantiacus M045.S. griseoaurantiacus M045 contains general secretory pathway and partial twin-arginine translocation pathway. The sortase and lipoprotein signal peptidase of S. griseoaurantiacus M045 are homologous with Salini.spora respectively, but not found in S. coelicolor A3(2), S. avermitilis MA-4680 and S. griseus IFO13350. S. griseoaurantiacus M045 has abundant functional genes for environmental adaptation, whole biosynthesis pathway of pyochelin for marine iron-limited environment and encoding gas vesicle synthesis protein for seawater adaptation.Genome analysis revealed a number of genes related to biosynthesis of secondary metabolites, including some involved in NRPS-PKS I fusion, PKS II and PKS III pathways. Manumycin A contains a 3-amino-4-hydroxybenzoic acid (3,4-AHBA) core component, two triene polyketide chains, and a 2-amino-3-hydroxycyclopent-2-enone (C5N) moiety. The gene cluster for manumycin A contains 32 genes, including 3-amino-4-hydroxybenzoic acid (3,4-AHBA) synthase,3,4-AHBA carrier protein,3-oxoacyl-(acyl carrier protein) synthase, and 5-aminolevulinate synthase. Chinikomycins contain a pABA core component, but share a partial gene cluster with manumycin A that consists of two triene polyketides and a 2-amino-3-hydroxycyclopent-2-enone biosynthetic pathway.S. griseoaurantiacus M045 is the first marine streptomycete for which a genome sequence has been reported. It is considered that this work provides insight into the functional adaptation and combinatorial biosynthesis of bioactive molecules produced by marine streptomycetes.