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Three new polycyclic macrolactams, cyclamenols B-D (1-3), together with a known macrolactam, cyclamenol A (4), were isolated from the Streptomyces sp. OUCMDZ-4348. Their structures including absolute configurations were determined on the basis of spectroscopic analysis, chemical methods, and ECD calculations. The biosynthetic pathways involving intramolecular Diels-Alder reactions were proposed. Compound 1 exhibited selective inhibition against the gastric carcinoma cell line N87 with an IC50 value of 10.8 μM.

Cyanogramide (1), an unprecedented alkaloid bearing a novel spirocyclic pyrrolo[1,2-c]imidazole skeleton, was identified from the fermentation broth of the marine-derived Actinoalloteichus cyanogriseus WH1-2216-6. The structure was fully determined by spectroscopic analysis, an exciton chirality CD method, and quantum mechanical calculations. Cyanogramide (1) could efficiently reverse the adriamycin-induced resistance of K562/A02 and MCF-7/Adr cells, and the vincristine-induced resistance of KB/VCR cells at a concentration of 5 μM, with the reversal fold values of 15.5, 41.5, and 9.7, respectively.

The biosynthetic gene cluster for caerulomycin A (1) was cloned and characterized from the marine actinomycete Actinoalloteichus cyanogriseus WH1-2216-6, which revealed an unusual hybrid polyketide synthase (PKS)/nonribosomal peptide synthetase (NRPS) system. The crmL disruption mutant accumulated caerulomycin L (2) with an extended L-leucine at C-7, implicating an amidohydrolase activity for CrmL. The leucine-removing activity was confirmed for crude CrmL enzymes. Heterologous expression of the 1 gene cluster led to 1 production in Streptomyces coelicolor.

Streptocarbazoles A (1) and B (2), two novel indolocarbazoles featuring unprecedented cyclic N-glycosidic linkages between 1,3-carbon atoms of the glycosyl moiety and two indole nitrogen atoms of the indolocarbazole core, were isolated from the marine-derived actinomycetes strain Streptomyces sp. FMA. Their structures were established by spectroscopic methods, CD spectra, and ECD quantum mechanical calculations. Compound 1 was cytotoxic on HL-60 and A-549 cell lines and could arrest the cell cycle of Hela cells at the G(2)/M phase.

Cyanogrisides A-D (1-4), four new glycosidic derivatives of bipyridine featuring a novel cyclic glycoside generated by vicinal hydroxyl groups of an aglycone with both the anomeric center and the adjacent carbonyl of a keto sugar, were isolated from the marine-derived actinomycete Actinoalloteichus cyanogriseus WH1-2216-6. The structures of 1-4 were elucidated by spectroscopic analysis, X-ray single crystal diffraction, CD spectra, and chemical methods.

Inactivation of the O-methyltransferase gene crmM of Actinoalloteichus cyanogriseus WH1-2216-6 led to a mutant that produced three new acyclic bipyridine glycosides, cyanogrisides E-G (1-3). Further chemical analysis of the wild strain yielded 1 and another new analogue, cyanogriside H (4). Compounds 1-4 possess a skeleton consisting of a 2,2'-bipyridine and a D-quinovose or L-rhamnose sugar moiety. Cyanogriside G (3) was considered to be a key biosynthetic intermediate of the cyclic bipyridine glycosides cyanogrisides A-D. Compounds 2 and 3 showed cytotoxicities against HCTI16 and HL-60 cells, and compounds 1 and 4 were cytotoxic on K562 cells.

Fradcarbazoles A-C (1-3), three new indolocarbazoles, were isolated from a mutant strain of the marine-derived actinomycete Streptomyces fradiae 007M135. Their structures were established by spectroscopic analysis, quantum chemical calculation, CD spectra, and chemical transformation. Fradcarbazole A (1) possessed a unique skeleton consisting of a staurosporine core, a thiazole ring, and an indole fragment. Compounds 1-3 displayed significant cytotoxicity against HL-60, K562, A-549, and BEL-7402 cell lines and inhibitory effects on the kinase PKC-α with IC(50) values of 0.001-4.58 μM.

Cottoquinazoline D (3), a new alkaloid with a 1-aminocyclopropane-1-carboxylic acid residue rarely discovered in nature, was isolated and identified together with two new quinazolinone alkaloids, cottoquinazolines B (1) and C (2), from coral-associated fungus Aspergillus versicolor LCJ-5-4. Their structures including absolute configurations were elucidated based on spectroscopic methods, X-ray single crystal diffraction analysis, and chemical methods. A possible biogenetic pathway for them was proposed.

Two novel cyclic hexapeptides containing both anthranilic acid and dehydroamino acid units, sclerotides A (1) and B (2), were isolated from the marine-derived halotolerant Aspergillus sclerotiorum PT06-1 in a nutrient-limited hypersaline medium. Both 1 and 2 are photointerconvertible and could be interconverted via a radical reaction initiated by direct photoisomerization. Both compounds showed moderate antifungal activity. Compound 2 also showed weak cytotoxicity and antibacterial activity.