Absolute configuration of iminimycin B, a new indolizidine alkaloid, from  Streptomyces griseus  OS-3601

Nakashima, Takuji; Miyano, Rei; Matsuo, Hirotaka; Iwatsuki, Masato; Shirahata, Tatsuya; Kobayashi, Yoshinori; Shiomi, Kazuro; Petersson, George A.; Takahashi, Yōko; Ōmura, Satoshi

doi:10.1016/j.tetlet.2016.06.040

Cited by 16 publications

(10 citation statements)

References 18 publications

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“…With respect to the three entries in question, the name of the original compound and retention period by lyophilization are stated, all three having been stored for 35 years or more. The compounds recently discovered, namely bisoxazolomycin [ 32 ], the iminimycins [ 33 , 34 ], and the nanaomycins [ 35 , 36 ], would probably not have been detected by an assay system seeking a specific bioactive property, the compounds being found as a direct result of PC screening. Discovery of the iminimycins and nanaomycins are described in detail below in Section 4.2 .…”

Section: Novel Compounds Discovered By Physicochemical (Pc) Screenmentioning

confidence: 99%

“…An unidentified compound with physical and chemical properties similar to iminimycin A was observed in the octadecyl silyl fraction lacking iminimycin A; the compound having an 399.1736 m/z [M + H] + and maximal absorption at 269 and 282 nm. Purification of this compound revealed a new indolizine alkaloid, designated iminimycin B ( Figure 1 ) [ 34 ], that possessed N -acetylcysteine and pyridinium moieties, instead of the iminium moiety of iminimycin A. Iminimycin A and B both show antimicrobial activity against Gram-positive and Gram-negative bacteria. Since 1943, when Selman A. Waksman discovered streptomycin from the secondary metabolite of Streptomyces griseus , about 200 compounds have been reported from strains identified as Streptomyces griseus [ 9 ].…”

Section: Novel Compounds Discovered From the Kitasato Microbial LImentioning

confidence: 99%

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Actinomycetes, an Inexhaustible Source of Naturally Occurring Antibiotics

2018

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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.

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Section: Novel Compounds Discovered By Physicochemical (Pc) Screenmentioning

confidence: 99%

Section: Novel Compounds Discovered From the Kitasato Microbial LImentioning

confidence: 99%

Actinomycetes, an Inexhaustible Source of Naturally Occurring Antibiotics

2018

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“…When IFO13350 was incubated in three different media (SMM, Q medium, and iminimycin production medium), we detected two compounds with m/z corresponding to iminimycins A and B in all three media (Figure S1). [14,15] The compound corresponding to iminimycin A was further analyzed by NMR analysis after reduction using sodium borohydride (NaBH 4 ) and purification (Table S1, Figures S10-S14). These experiments clearly showed that IFO13350 also produces iminimycins A and B.…”

Section: Identification Of Iminimycin Biosynthetic Gene Clustermentioning

confidence: 99%

“…For example, dehydrogenation of tetrahydroberberine in berberine biosynthesis results in the formation of a pyridine ring with an iminium cation [17] . In Streptomyces , the iminium cation is very rare and is only observed in indolizidine alkaloids and ammosamide derivatives [14,15,19–22] . While the iminium moiety of ammosamide derivatives was predicted to be biosynthesized by the N ‐methylation of an imine group, [20,21] how the iminium moiety is biosynthesized in indolizidine alkaloids remains unclear.…”

Section: Introductionmentioning

confidence: 99%

“…Iminimycins A and B are indolizidine alkaloids discovered from Streptomyces griseus OS-3601, which is known as a producer of streptomycin, through physicochemical screening (Figure 1a). [14,15] Iminimycin A contains an unusual iminium cation and a cyclopropane ring fused with an indolizidine structure (6-5-3 tricyclic structure). Iminimycin B is a derivative of iminimycin A with a pyridinium ring and an N-acetyl-cysteine moiety.…”

Section: Introductionmentioning

confidence: 99%

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Identification and Analysis of the Biosynthetic Gene Cluster for the Indolizidine Alkaloid Iminimycin in Streptomyces griseus

et al. 2021

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Indolizidine alkaloids, which have versatile bioactivities, are produced by various organisms. Although the biosynthesis of some indolizidine alkaloids has been studied, the enzymatic machinery for their biosynthesis in Streptomyces remains elusive. Here, we report the identification and analysis of the biosynthetic gene cluster for iminimycin, an indolizidine alkaloid with a 6‐5‐3 tricyclic system containing an iminium cation from Streptomyces griseus. The gene cluster has 22 genes, including four genes encoding polyketide synthases (PKSs), which consist of eight modules in total. In vitro analysis of the first module revealed that its acyltransferase domain selects malonyl‐CoA, although predicted to select methylmalonyl‐CoA. Inactivation of seven tailoring enzyme‐encoding genes and structural elucidation of four compounds accumulated in mutants provided important insights into iminimycin biosynthesis, although some of these compounds appeared to be shunt products. This study expands our knowledge of the biosynthetic machinery of indolizidine alkaloids and the enzymatic chemistry of PKS.

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