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A large number of novel bioactive compounds were discovered from microbial secondary metabolites based on the traditional bioactivity screenings. Recent fermentation studies indicated that the crude extract of marine Streptomyces sp. W007 possessed great potential in agricultural fungal disease control against Phomopsis asparagi, Polystigma deformans, Cladosporium cucumerinum, Monilinia fructicola, and Colletotrichum lagenarium. To further evaluate the biosynthetic potential of secondary metabolites, we sequenced the genome of Streptomyces sp. W007 and analyzed the identifiable secondary metabolite gene clusters. Moreover, one gene cluster with type II PKS implied the possibility of Streptomyces sp. W007 to produce aromatic polyketide of angucyclinone antibiotics. Therefore, two novel compounds, 3-hydroxy-1-keto-3-methyl-8-methoxy-1,2,3,4-tetrahydro-benz[α]anthracene and kiamycin with potent cytotoxicities against human cancer cell lines, were isolated from the culture broth of Streptomyces sp. W007. In addition, other four known angucyclinone antibiotics were obtained. The gene cluster for these angucyclinone antibiotics could be assigned to 20 genes. This work provides powerful evidence for the interplay between genomic analysis and traditional natural product isolation research.

A new anthracene derivative, 3-hydroxy-1-keto-3-methyl-8-methoxy-1,2,3, 4-tetrahydro-benz[alpha]anthracene, was isolated from the marine strain Streptomyces sp. W007, and its structure was established by spectroscopic analysis including mass spectra, 1D- and 2D-NMR ((1)H-(1)H COSY, HMBC, HSQC and NOESY) experiments. 3-hydroxy-1-keto-3-methyl-8-methoxy-1,2,3,4-tetrahydro-benz[alpha]anthracene showed cytotoxicity against human lung adenocarcinoma cell line A549.

Marine Streptomyces are potential candidates for novel natural products and industrial catalysts. In order to set up biosynthesis approach for a holomycin-producing strain M095 isolated from Jiaozhou Bay, China, a genetic transformation system was established using intergeneric conjugation. The plasmid pIJ8600 consists of an origin of replication for Escherichia coli, a phage integrase directing efficient site-specific integration in bacterial chromosome, thiostrepton-induced promoter and an attP sequence. Using E. coli ET12567 (pUZ8002) carrying pIJ8600 as a conjugal donor, while it was mated with strain M095, pIJ8600 was mobilized to the recipient and the transferred DNA was also integrated into the recipient chromosome. The frequency of exconjugants was 1.9+/-0.13x10(-4) per recipient cell. Analysis of eight exconjugants showed pIJ8600 was stable integrated at a single chromosomal site (attB) of the Streptomyces genome. The DNA sequence of the attB was cloned and shown to be conserved. The results of growth and antimicrobial activity analysis indicated that the integration of pIJ8600 did not seem to affect the biosynthesis of antibiotics or other essential amino acids. To demonstrate the feasibility of above gene transfer system, the allophycocyanin gene (apc) from cyanobacterium Anacystis nidulans UTEX625 was expressed in strain M095, and the results indicated heterologous allophycocyanin could be expressed and folded effectively.

In our screening of micro-organisms for novel bioactive natural products, a new staurosporinone, N-carboxamido-staurosporine (1c), and a new sesquiterpene, (5S,8S,9R, 10S)-selina-4(14),7(11)-diene-8,9-diol (2a), were isolated from the culture broth of the marine-derived Streptomyces sp. QD518. Their structures were determined by spectroscopic methods and by comparison of the NMR data with those of structurally related known natural products, which were isolated from the same strain.

Allophycocyanin is one of the most important marine active peptides. Previous studies suggested that recombinant allophycocyanin (rAPC) could remarkably inhibit the S-180 carcinoma in mice, indicating its potential pharmaceutical uses. Based on intergeneric conjugal transfer, heterologous expression of rAPC was first achieved in marine Streptomyces sp. isolate M097 through inserting the apc gene into the thiostrepton-induced vector pIJ8600. The transformation frequency for this system was approximately 10−4 exconjugants/recipient. In the transformed Streptomyces sp. isolate M097, the yield of purified rAPC could amount to about 38 mg/l using a simple purification protocol, and HPLC analysis showed that the purity of the protein reached about 91.5%. In vitro activity tests also revealed that the purified rAPC had effective scavenging abilities on superoxide and hydroxyl radicals. This would widen the usefulness of the marine Streptomyces as a host to express the rAPC and to offer industrial strain for the production of rAPC.

In our screening of marine Streptomycetes for bioactive principles, two novel antitumor antibiotics designated as chinikomycins A (2a) and B (2b) were isolated together with manumycin A (1), and their structures were elucidated by a detailed interpretation of their spectra. Chinikomycins A (2a) and B (2b) are chlorine-containing aromatized manumycin derivatives of the type 64-pABA-2 with an unusual para orientation of the side chains. They exhibited antitumor activity against different human cancer cell lines, but were inactive in antiviral, antimicrobial, and phytotoxicity tests.

The chemical investigation of the crude extract of the marine-derived Streptomyces sp. M491 yielded three new sesquiterpenes, namely, 10 alpha,11-dihydroxyamorph-4-ene (4), 10 alpha,15-dihydroxyamorph-4-en-3-one (6), and 5 alpha,10 alpha,11-trihydroxyamorphan-3-one (7). In addition, the known compounds 10 alpha-hydroxyamorph-4-en-3-one (2), o-hydroxyacetanilide, genistein, prunetin, and indole-3-carbaldehyde and the macrolide antibiotic chalcomycin A were identified. The structures were determined on the basis of spectroscopic analysis, especially 1D and 2D NMR data. This is the first report of these sesquiterpenes from bacteria.

The chemical investigation of the crude extract of the marine-derived Streptomyces sp. M491 yielded three new sesquiterpenes, namely, 10alpha,11-dihydroxyamorph-4-ene (4), 10alpha,15-dihydroxyamorph-4-en-3-one (6), and 5alpha,10alpha,11-trihydroxyamorphan-3-one (7). In addition, the known compounds 10alpha-hydroxyamorph-4-en-3-one (2), o-hydroxyacetanilide, genistein, prunetin, and indole-3-carbaldehyde and the macrolide antibiotic chalcomycin A were identified. The structures were determined on the basis of spectroscopic analysis, especially 1D and 2D NMR data. This is the first report of these sesquiterpenes from bacteria.

A series of angucyclinone antibiotics have been isolated from marine Streptomyces sp. strain W007 and identified. Here, a draft genome sequence of Streptomyces sp. W007 is presented. The genome contains an intact biosynthetic gene cluster for angucyclinone antibiotics, which provides insight into the combinatorial biosynthesis of angucyclinone antibiotics produced by marine streptomycetes.

Streptomyces griseoaurantiacus M045, isolated from marine sediment, produces manumycin and chinikomycin antibiotics. Here we present a high-quality draft genome sequence of S. griseoaurantiacus M045, the first marine Streptomyces species to be sequenced and annotated. The genome encodes several gene clusters for biosynthesis of secondary metabolites and has provided insight into genomic islands linking secondary metabolism to functional adaptation in marine S. griseoaurantiacus M045.