Actinomycetes, an Inexhaustible Source of Naturally Occurring Antibiotics

Abstract

Global public health faces a desperate situation, due to the lack of effective antibiotics. Coordinated steps need to be taken, worldwide, to rectify this situation and protect the advances in modern medicine made over the last 100 years. Work at Japan’s Kitasato Institute has been in the vanguard of many such advances, and work is being proactively tailored to promote the discovery of urgently needed antimicrobials. Efforts are being concentrated on actinomycetes, the proven source of most modern antibiotics. We devised a novel physicochemical screening mechanism, whereby simple physico-chemical properties, in conjunction with related detection methods, such as LC/MS, LC/UV, and polarity, could be used to identify or predict new compounds in a culture broth, simply by comparing results with existing databases. New compounds are isolated, purified, and their structure determined before being tested for any bioactivity. We used lyophilized actinomycete strains from the Kitasato Microbial Library, most more than 35 years old, and found 330 strains were producers of useful bioactive substances. We also tested organisms found in fresh samples collected in the complex environments from around plant roots, as well as from sediments of mangrove forests and oceans, resulting in the discovery of 36 novel compounds from 11 actinomycete strains. A compound, designated iminimycin, containing an iminium ion in the structure was discovered from the culture broth of Streptomyces griseus OS-3601, which had been stored for a long time as a streptomycin-producing strain. This represented the first iminium ion discovery in actinomycetes. Compounds with a cyclopentadecane skeleton containing 5,6-dihydro-4-hydroxyl-2-pyrone ring and tetrahydrofuran ring, designated mangromicins, were isolated from the culture broth of Lechevalieria aerocolonigenes K10-0216 obtained from sediment in a mangrove forest. These structures are extremely unique among natural compounds. From the same culture broth, new steroid compounds, named K10-0216 KA and KB, and other new compounds having a thiazole and a pyridine ring, named pyrizomicin A and B, were discovered. New substances can be found from actinomycetes that have been exhaustively studied. Novel compounds with different skeletons can be found from a single broth of one strain. The sought after new antibiotics will arise from continued exploitation of the actinomycetes, especially rare actinomycetes. Work on new organisms and samples should be augmented by re-examination of known actinomycetes already in storage. New research should also be carried out on the manipulation of culture media, thereby stimulating actinomycete strains to produce novel chemicals. The establishment of wide-ranging international research collaborations will facilitate and expedite the efficient and timely discovery and provision of bioactive compounds to help maintain and promote advances in global public health.

Potentially pathogenic bacteria isolated from diverse habitats in Spitsbergen, Svalbard

“…Actinobacteria species are generally regarded as an abundant source of metabolites such as antibiotics, antioxidants, and hemolytic as well as anti-hemolytic compounds (Goodfellow et al 2009;Suthindhiran and Kannabiran 2009;Pang et al 2016). We observed members of the genera Micromonospora, Streptomyces, and Oerskovia (isolates S3, S10, N18, N28, and N41) that exhibited hemolytic activity, supporting previous reports of species in these genera that might be considered opportunistic pathogens (McNeil and Brown 1994;Pang et al 2016;Mohammadipanah and Momenilandi 2018;Takahashi and Nakashima 2018).…”

Streptomyces spp. From the Marine Sponge Antho dichotoma: Analyses of Secondary Metabolite Biosynthesis Gene Clusters and Some of Their Products

“…These bacteria remain of significant interest in terms of discovery of biologically active secondary metabolites that can potentially be developed into human medicines such as antimicrobial and anticancer agents, immunosuppressants etc. (Takahashi and Nakashima, 2018). The unprecedented genetic potential of Streptomyces to produce diverse secondary metabolites is exemplified by a large number (usually 20-40) of biosynthetic gene clusters harbored by their genomes (Baltz, 2017).…”

Characterization of Endophytic Streptomyces griseorubens MPT42 and Assessment of Antimicrobial Synergistic Interactions of Its Extract and Essential Oil from Host Plant Litsea cubeba

“…Since many novel antibiotics exhibiting strong effects against multiple-drug resistant bacteria have been isolated from medicinal plant-associated endophytic Streptomyces spp. in the last decades [22,[25][26][27][28], endophytic S. griseorubens MP42 could be a potential candidate for the production of valuable bioactive substances.…”