Fermentation Optimization of the Caerulomycin H and the Synthesis of Cyanogriside K

Abstract

Caerulomycin H (2) and its 4-yl α-L-rhamnopyranoside [cyanogriside K (1)] are two microbial natural products from marine-derived Actinoalloteichus cyanogriseus WH1-2216-6. Cyanogriside K (1) shows good antiproliferative activity against tumor cells, whereas the yield is very low and the synthesis has not been reported. Thus, enough caerulomycin H (2) was first obtained by optimazing the fermentation condition of the mutant strain CRM05 of A. cyanogriseus WH1-2216-6. The yield of caerulomycin H (2) reached 272 mg/L (increased by 5 times) in the optimal solid medium consisted of corn pellets (80 g) and liqiud medium 5# for actinomycetes (100 mL). Then cyanogriside K (1) was synthesized with 25.6% total yield from caerulomycin H (2) by six steps reactions including deoximation, rhamnosylation, oximation and deacetylation. The structure of cyanogriside K (1) was identified by NMR, HRESIMS and specific rotation data. It is the same compound as the reported natural product. Furthermore, cyanogriside K (1) showed good bioactivity against the proliferation of the tumor cell lines PA-TU8988T, 786-O, 5673, DU145, A-375, FaDu and SF126, with the half maximal inhibitory concentration (IC50) values ranging from 1.07 μmol/L to 1.78 μmol/L.