Absolute Configurations of Macrolide Antibiotics of the Bafilomycin and Leucanicidin Groups.

O’Shea, Michael G.; Rickards, Rodney W.; Rothschild, Jennifer M.; Lacey, Ernest

doi:10.7164/antibiotics.50.1073

Cited by 21 publications

(9 citation statements)

References 18 publications

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“…In early 1980s, two macrolides were discovered: one was bafilomycin showing antifungal activity (Werner et al 1984) and the other concanamycin screened as an immunosuppressive compound (Kinashi et al 1984). Later some other compounds in this category were further found from nature, including hygrolidin (Seto et al 1984), setamycin (Otoguro et al 1988), leucancidin (O’Shea et al 1997), micromonospolide (Ohta et al 2001), and so on.…”

Section: Introductionmentioning

confidence: 99%

Organization and characterization of a biosynthetic gene cluster for bafilomycin from Streptomyces griseus DSM 2608

Hwang

Kim

et al. 2013

AMB Express

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Streptomyces griseus DSM 2608 produces bafilomycin, an antifungal plecomacrolide antibiotic. We cloned and sequenced an 87.4-kb region, including a polyketide synthase (PKS) region, methoxymalonate genes, flavensomycinate genes, and other putative regulatory genes. The 58.5kb of PKS region consisting 12 PKS modules arranged in five different PKS genes, was assumed to be responsible for the biosynthesis of plecomacrolide backbone including 16-membered macrocyclic lactone. All the modules showed high similarities with typical type I PKS genes. However, the starting module of PKS gene was confirmed to be specific for isobutyrate by sequence comparison of an acyltransferase domain. In downstream of PKS region, the genes for methoxymalonate biosynthesis were located, among which a gene for FkbH-like protein was assumed to play an important role in the production of methoxymalonyl-CoA from glyceryl-CoA. Further the genes encoding flavensomycinyl-ACP biosynthesis for the post-PKS tailoring were also found in the upstream of PKS region. By gene disruption experiments of a dehydratase domain of module 12 and an FkbH-like protein, this gene cluster was confirmed to be involved in the biosynthesis of bafilomycin.

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Section: Introductionmentioning

confidence: 99%

Organization and characterization of a biosynthetic gene cluster for bafilomycin from Streptomyces griseus DSM 2608

Hwang

Kim

et al. 2013

AMB Express

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“…It was later established by X-ray crystallographic analyses of the 21-(2',2',2'-trichloroethylcarbonate derivative of 2a [3c] and 2a itself [3d]. Through chemical conversion and analysis of spectroscopic data, Richards [23] established the complete absolute stereochemistry for bafilomycin B 1 (2b), bafilomycin C 1 (2c), bafilomycin A 1 21-O-(α-Lrhamnopyranoside) (2d), and leucanicidin (2e).…”

Section: Structures Of Selected Plecomacro-lidesmentioning

confidence: 99%

Structures and Total Syntheses of the Plecomacrolides

Dai

Guan²,

Jin

2005

CMC

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The plecomacrolides are a large family of natural products typically featured with a 16- or 18-membered macrolactone possessing two conjugated diene units and a hemiacetal side chain. The macrocycle skeleton is connected with the side chain through a three-carbon linker, forming a biologically important intramolecular hydrogen bonding network among the lactone/linker/hemiacetal structural motif. Many members of the plecomacrolides act as selective inhibitors of vacuolar H+-ATPases (V-ATPases) and they are considered to have the potential for treatment of postmenopausal osteoporosis. Significant progress has been achieved in recent years in the area of plecomacrolide total synthesis. These include the total synthesis of bafilomycin A1 by Evans, Toshima, Hanessian, and Roush, of bafilomycin V1 by Marshall, of hygrolidin by Hashimoto and Yonemitsu, of concanamycin F by Paterson and Toshima, and of formamicin by Roush. The synthetic strategies and key transformations used in the total synthesis are discussed.

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“…(Figure 2b) indicated that they could be assigned as 2E, 4E, 6R*, 7S*, 8S*, 14S*, 15R* and 16S*, showing the same stereochemistry as those of bafilomycins reported previously. 13 However, the stereochemistry of C-23 was not elucidated by the ROESY experiments. For elucidation of the absolute stereochemistry, we need more investigations.…”

Section: Stereochemistry Of Bflmentioning

confidence: 99%

Bafilomycin L, a new inhibitor of cholesteryl ester synthesis in mammalian cells, produced by marine-derived Streptomyces sp. OPMA00072

et al. 2014

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Marine-derived Streptomyces sp. OPMA00072 was found to produce inhibitors of the synthesis of neutral lipids in a cell-based assay using Chinese hamster ovary (CHO) cells. A new 16-membered macrolide named bafilomycin L (BFL) (1) was isolated along with the known structurally related bafilomycin C1 (BFC1) (3) from the culture broth of the actinomycete by solvent extraction, octadecylsilyl column chromatography and HPLC. BFL inhibited cholesteryl ester (CE) synthesis in CHO cells with an IC50 value of 0.83 nM and also in mouse peritoneal macrophages with an IC50 of 6.1 nM. In addition, BFL blocked cellular acidification in HeLa cells by interfering with vacuolar H(+)-ATPase (V-ATPase) as well as other bafilomycins. These data strongly suggest that BFL disturbed the lysosome function to block cholesterol metabolism, leading to the inhibition of CE accumulation in mammalian cells.

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Absolute Configurations of Macrolide Antibiotics of the Bafilomycin and Leucanicidin Groups.

Cited by 21 publications

References 18 publications

Organization and characterization of a biosynthetic gene cluster for bafilomycin from Streptomyces griseus DSM 2608

Organization and characterization of a biosynthetic gene cluster for bafilomycin from Streptomyces griseus DSM 2608

Structures and Total Syntheses of the Plecomacrolides

Bafilomycin L, a new inhibitor of cholesteryl ester synthesis in mammalian cells, produced by marine-derived Streptomyces sp. OPMA00072

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