Antitumor Compounds from Actinomycetes in Deep-sea Water of Toyama Bay

Abstract

Actinomycetes are the richest source of bioactive small molecules with high structural complexity and diversity which have been an inspiration to drug development. After the intensive screening efforts from soil-derived actinomycetes over a half century, it became necessary to exploit new microbial resources for discovering new drug leads. The deep-sea water in Toyama Bay is known as the 'specific deep-sea water of Japan Sea' because Sea of Japan is almost enclosed from the Pacific Ocean and the water exchanges very slowly with the neighboring seas. Furthermore, high dissolved oxygen concentration in this sea water gives rise to high biological productivity. As a part of investigation on the deep-sea water in Toyama Bay, we undertook the isolation of actinomycetes from deep-sea water for evaluation of bioactive compound production. This chapter summarizes the chemistry and biology of antitumor compounds produced by actinomycetes collected from the deep-sea water in Toyama Bay.Keywords Actinomycetes · Micromonospora · Deep-sea water · Antitumor compounds IntroductionToyama Bay is located in the northern shores of Honshu, Japan, and faced to Sea of Japan. The sea water present deeper than 300 m is called 'deep-sea water', which occupies about 60 % of the total volume of Toyama Bay. The deep-sea water of Toyama Bay has a low temperature, annually stable around 2 °C. The salinity is also stable at 34.0-34.1 g/kg, higher than that of surface sea water (32-33 g/kg). Utilization of the deep-sea water is being studied for commercial/industrial purposes such as aquatic culture of cold-water shrimps. As a part of investigation on the deep-sea water in Toyama Bay, we undertook the isolation of actinomycetes from

A New Micromonospora Strain with Antibiotic Activity Isolated from the Microbiome of a Mid-Atlantic Deep-Sea Sponge

“…Experiments using knockout strains suggested that resistance in other Gram-negative strains was mediated by efflux. Isoquinocycline B was also toxic to the HepG2 liver cancer cell line, in agreement with the anticancer properties of kosinostatin highlighted by Igarashi et al [ 29 ]. The mechanism of cytotoxicity is indicated to be by inhibition of DNA topoisomerase [ 14 ], similar to other DNA intercalators such as the aromatic polyketides daunorubicin and doxorubicin, which have a similar anthracycline core [ 30 ].…”