Efficient biotransformations in Cunninghamella elegans and Streptomyces sp. JCM9888 of selectively fluorinated benzoic acids to the corresponding benzamides and benzyl alcohols

Support was received from the Commonwealth Scholarship Council for a Split Site Studentship (OO) and also from the Royal Society of Chemistry for a travel Grant (C.I).An efficient conversion of ortho, meta and para fluoro- and trifluoromethyl-substituted benzoic acids to the corresponding benzamides in fermentations of the soil bacterium Streptomyces sp. JCM9888 is described. We also report the efficient reduction of the same class of substrates to the corresponding benzyl alcohols with the fungi Cunninghamella elegans. These biotransformations were surprisingly efficient and may have value as disruptive technologies in process chemistry.Publisher PDFPeer reviewe

The degradation of coniferyl alcohol and the complementary production of chlorogenic acids in the growth culture of Streptomyces albogriseolus KF977548 isolated from decaying wood residues

Coniferyl alcohol is one of the major precursors of lignin; the most abundant aromatic compound and a natural resource currently receiving attention because of the value-added metabolites resulting from its degradation. Growth study of Streptomyces albogriseolus KF977548 (strain AOB) isolated from decaying wood residues in a tropical estuarine ecosystem was carried out using coniferyl alcohol as a sole carbon source. Cell growth and metabolite production were monitored at 24 h interval by dry weight measurements and HPLC, LC–MS-DAD analyses. Biochemical and PCR assays were carried out to detect the major catabolic enzymes of interest. Strain AOB utilized coniferyl alcohol completely within 72 h ( = 0.204 h−1, Td = 3.4 h). Laccase and peroxidase were released into the growth medium up to 0.099 and 98 mol/mL respectively. Protocatechuate 3, 4-dioxygenase and demethylase were detected in the genome whilst ortho-adipate pathway was clearly indicated. Growth on coniferyl alcohol or caffeic acid as mono substrates resulted in the production of secondary metabolites identified by HPLC–MS as 1- caffeoylquinic and 3,4,5-tricaffeoylquinic acids, known as chlorogenic acids, in the culture medium. The microbial production of chlorogenic acids from a lignin-related substrate base by strain AOB could arouse a plausible biotechnological process

Sustainable generation of bioethanol from sugarcane wastes by Streptomyces coelicolor strain COB KF977550 isolated from a tropical estuary

The damaging effect and challenges associated with the use of fossil fuel is enormous and very costly. Biofuels could be obtained from plant biomass wastes which are known to be sources of environmental pollution and breeding grounds for vectors of diseases. Sugarcane bagasse was exploited as a renewable substrate for obtaining bioethanol using Streptomyces strain COB KF977550 as inoculum. Submerged aerobic batch fermentation was performed in flasks containing mineral salts medium supplemented with 5.0 g (w/v) sugarcane bagasse. Incubation was done in a shaker (150 rpm) at 30 oC for 21 days. Microbial growth was assessed by measurement of the optical density (O.D 600nm) at 3-day intervals. Fractional distillation was carried out in batch mode using a simple fractional distillation setup. Metabolic products were determined using GC-FID. Further analyses were performed using FTIR and GC-MS. The optical density of S.coelicolor strain COB KF977550 increased from 0.9 to 1.41. The GC-FID showed that 43.08 g/L ethanol was generated. Interestingly, the results showed the presence of diverse biochemicals released into the medium in addition to the main product ethanol. Ten carboxylic acids including formic acid, glycolic acid, tartaric acid, acetic acid, citric acid, oxalic acid, malic acid, lactic acid, n-valeric acid, and 3-hydroxybutyric acid were identified as biochemical organic acids by-products

Aryl (β, β', β''-trifluoro)-tert-butyl : a candidate motif for the discovery of bioactives

Funding: UK Engineering and Physical Sciences Research Council - EP/S030506/1; Commonwealth Scholarship Commission.The (β,β′,β″-trifluoro)-tert-butyl (TFTB) group has received very little attention in the literature. This work presents a direct synthesis of this group and explores its properties. The TFTB group arises when the methyl groups of a tert-butyl moiety are exchanged for fluoromethyl groups. Sequential fluoromethylations result in a decrease of Log P (increasing hydrophilicity), ultimately by 1.7 Log P units in the TFTB group relative to that of tert-butyl benzene itself. A focus is placed on synthetic transformations, conformational analysis, and metabolism of the TFTB group in the context of presenting a favorable profile as a motif for the discovery of bioactives.Publisher PDFPeer reviewe

(β-D-ribofuranosyl)formamidine in the design and synthesis of 2-(β-D-ribofuranosyl)pyrimidines, including RF-containing derivatives

A wide range of novel 2-(β-D-ribofuranosyl)pyrimidines, including RF-containing derivatives, have been synthesized by the reaction of (β-D-ribofuranosyl)formamidine with various dielectrophilic substrates such as 3-alkoxy- and 3-chloro-1-(polyfluoroalkyl)propen-1-ones, 3-nitro- and 3-(phenylethynyl)chromones and heteroaryl acetylenic ketones. Polyfluoroalkyl-containing 2-(β-D-ribofuranosyl)pyrimidine derivatives have been synthesized by the reaction of (β-D-ribofuranosyl)formamidine with dielectrophilic substrates such as 3-alkoxy- and 3-chloro-1-(polyfluoroalkyl) propen-1-ones, 3-nitro- and 3-(phenylethynyl)chromones and heteroaryl acetylenic ketones. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Cryptophycins: cytotoxic cyclodepsipeptides with potential for tumor targeting

Weiss C, Figueras Agustí E, Borbély AN, Sewald N. Cryptophycins: cytotoxic cyclodepsipeptides with potential for tumor targeting. Journal of Peptide Science. 2017;23(7-8):514-531.Cryptophycins are a class of 16-membered highly cytotoxic macrocyclic depsipeptides isolated from cyanobacteria. The biological activity is based on their ability to interact with tubulin. They interfere with microtubule dynamics and prevent microtubules from forming correct mitotic spindles, which causes cell-cycle arrest and apoptosis. Their strong antiproliferative activities with 100-fold to 1000-fold potency compared with those of paclitaxel and vinblastine have been observed. Cryptophycins are highly promising drug candidates, as their biological activity is not negatively affected by P-glycoprotein, a drug efflux system commonly found in multidrug-resistant cancer cell lines and solid tumors. Cryptophycin-52 had been investigated in phase II clinical trials but failed because of its high neurotoxicity. Recently, cryptophycin conjugates with peptides and antibodies have been developed for targeted delivery in tumor therapy. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd