Stereo-controlled synthesis of prelasalocid, a key precursor proposed in the biosynthesis of polyether antibiotic lasalocid A

In the biosynthesis of a polyether ionophore antibiotic, lasalocid A, the cyclic ether skeleton composed of a tetrahydrofuran linked to a tetrahydropyran could be constructed by oxidative cyclization of linear dodecaketide diene precursor. Hence, we hypothesized a prelasalocid having (E,E)-trisubstituted olefins as the dodecaketide biosynthetic precursor. A stereo-controlled synthetic route to the prelasalocid has been devised in a highly convergent manner entailing installation of a variety of substituents at the trisubstituted olefins.     

The structures of three new Galbulimima alkaloids

The structures of three new alkaloids isolated from the bark of the rain forest tree Galbulimima belgraveana, have been determined by a combination of NMR spectroscopy and X-ray crystallography. One of the alkaloids, himgrine (5), was shown to be an oxygenated derivative of himbacine (1), while the second, GB16, (8) proved to be identical with a degradation product from himgaline (4). The remaining alkaloid, GB17 (12) possesses an entirely new and unexpected skeleton.     

Microencapsulated mycelium-bound tannase from Aspergillus niger

Microencapsulated Aspergillus niger with mycelium-bound tannase activity was employed to investigate the esterification of propyl gallate from gallic acid and propanol in organic solvents. The effects of various organic solvents (log P:−1.0 to 6.6) on the enzymatic reactions showed that benzene (log P:2.0) was the suitable solvent, for which the conversion reached 26.8%. The optimum catalyst concentration and water concentration was found at 25 capsules in 10 mL of benzene and 0.04 g of water/capsule. The external mass transfer effect could be eliminated at stirring speeds of 180 rpm or higher. Both substrates 1-propanol and gallic acid had significant inhibition effects on the tannase activity. Maximum molar conversion (36.2%) was achieved with 9.1% (v/v) 1-propanol and 8 mM gallic acid and decreased with increasing amounts of substrates.     

Coordination of Polyketide Release and Multiple Detoxification Pathways for Tolerable Production of Fungal Mycotoxins

Efficient biosynthesis of microbial bioactive natural products (NPs) is beneficial for the survival of producers, while self-protection is necessary to avoid self-harm resulting from over-accumulation of NPs. The underlying mechanisms for the effective but tolerable production of bioactive NPs are not well understood. Herein, in the biosynthesis of two fungal polyketide mycotoxins aurovertin E ( 1 ) and asteltoxin, we show that the cyclases in the gene clusters promote the release of the polyketide backbone, and reveal that a signal peptide is crucial for their subcellular localization and full activity. Meanwhile, the fungus adopts enzymatic acetylation as the major detoxification pathway of 1 . If intermediates are over-produced, the non-enzymatic shunt pathways work as salvage pathways to avoid excessive accumulation of the toxic metabolites for self-protection. These findings provided new insight into the interplay of efficient backbone release and multiple detoxification strategies for the production of fungal bioactive NPs.     

Selective conversion of an enantioenriched cyclononadienone to the xeniolide, xenibellol, and florlide cores: an integrated routing strategy

Members of the xenicane superfamily induce a variety of biological responses in vitro. In order to enable a better understanding of the function of these substances, we have developed a strategy that integrates the synthetic routes to many of its members. The core ring systems of the xeniolide, xenibellol, and florlide natural products were constructed stereoselectively from an enantioenriched cyclononadienone. The use of the cyclononadiene scaffold, reagent-controlled transannulations, and the parallels of these transformations to possible biosynthetic pathways of the natural product classes are discussed.     

In situ biosynthesized silver nanoparticle-incorporated synthesized zeolite A using Orthosiphon aristatus extract for in vitro antibacterial wound healing

The capability of synthesized zeolite A (SZ) to immobilize Ag ions (Ag-SZ) and Ag nanoparticles (AgNp-SZ) were comparatively studied. A novel approach of in situ biosynthesized AgNP-incorporated synthesized zeolite A (AgNp-SZ) was synthesized at an optimum volume of 0.4 mL of the Orthosiphon aristatus (O. aristatus) leaves plant extract (5%) using an in situ approach. In comparison, Ag-SZ was produced by loading the synthesized zeolite with Ag ions. All synthesized materials were characterized for their morphologies and physicochemical properties. The characterization analyses validate that the biosynthesized AgNP (<100 nm) using O. aristatus leaves extract was incorporated into the zeolite A. The antibacterial testing confirmed that these materials have antibacterial activity against Escherichia coli ATCC 11229 and Staphylococcus aureus ATCC 6538. MIC/MBC analysis demonstrated that in 0.9% saline solution, AgNP-SZ had higher antibacterial activity than Ag-SZ. The in vitro cell viability and migration assays were further examined towards human skin fibroblast cells HSF 1184. Results show that the materials are not cytotoxic to HSF 1184, and the biosynthesized AgNP-SZ promotes cell migration and proliferation higher than Ag-SZ. This research proved that the biocompatible antibacterial wound healing agent of AgNP-SZ can be synthesized using an in situ approach where the reduction process of Ag ions in the zeolite A can be performed using plant extract.     

Discovery and biosynthesis of thioviridamide-like compounds

Thioviridamide-like compounds are a unique subfamily of ribosomally synthesized and post-translationally modified peptide and contain characteristic thioamide bonds and S-[(Z)-2-aminovinyl]-D-cysteine (AviCys). Members of this family are active against a number of cancer cell lines. As a unique subgroup of RiPPs, the distribution, biosynthetic machinery and the mode of action of thioviridamide and related compounds remain largely unknown. In this review, we outlined recent advances in the discovery of thioviridamide-like peptide natural products and the effort in the elucidation of their biosynthetic origin.     

生物技术与高分子材料

在简要介绍生物合成技术的基础上,综述了生物技术在高分子材料领域中的应用,并探讨了该新技术的发展前景。     

Isolation, structural elucidation, and biosynthesis of 15-norlankamycin derivatives produced by a type-II thioesterase disruptant of Streptomyces rochei

Lankamycin, a 14-membered macrolide antibiotic, contains a 3-hydroxy-2-butyl side chain at C-13. To analyze the function of lkmE, which encodes type-II thioesterase in the lankamycin cluster, we carried out a gene disruption experiment. Disruption of lkmE resulted in a 70% decrease of lankamycin production concomitant with an accumulation of novel lankamycin derivatives (LM-NS01A and LM-NS01B), in which the C-13 side chain is replaced by a 1-carboxyethyl group. The biosynthetic origin of 1-carboxyethyl group was confirmed by incorporation of deuterium in [3-²H]3-methyl-2-oxobutyrate into the C-14 position. These results indicate that the biosynthesis of LM-NS01A and LM-NS01B starts from isobutyryl CoA in place of (S)-2-methylbutyryl CoA and LkmE removes the aberrantly loaded starter unit and restores lankamycin production.     

Study on the biosynthesis of the notoamides: Pinacol-type rearrangement of the isoprenyl unit in deoxybrevianamide E and 6-hydroxydeoxybrevianamide E

Two reverse-prenylated indole alkaloids, deoxybrevianamide E and 6-hydroxydeoxybrevianamide E, are proposed as biosynthetic precursors for advanced metabolites isolated from the marine-derived Aspergillus sp. In order to uncover the role of the alkaloids in the biosynthetic pathway, the feeding experiments of the [¹³C]₂-[¹⁵N]-labeled deoxybrevianamide E and 6-hydroxydeoxybrevianamide E were performed to afford the metabolites, which were produced by oxidation and successive pinacol-type rearrangement of the isoprenyl units.