A new cyclic heptapeptide containing J-aminobutyric acid in the ring, namely unguisin E (1), was isolated from the fermentation culture of Aspergillus sp. AF119. The structure was elucidated by spectroscopic analyses, including 1D and 2D NMR experiments, and HR ESI-Q-TOF mass spectrometry, and by comparison with those reported. Compound 1 was evaluated for its antimicrobial activities by the paper diffusion method.

Tubercularia sp. TF5 is an endophytic fungal strain isolated from the medicinal plant Taxus mairei. Previously, taxol has been detected in the fermentation products of this strain. However, it lost the capability of producing taxol after long-term laboratory culture. Herein, we tried to reactivate the production of taxol by protoplast mutations and genome shuffling. The protoplasts of Tub. sp. TF5 were prepared from its mycelia, and mutated by UV and NTG. The mutant strains regenerated from the mutated protoplasts were selected and classified into four groups on the basis of their phenotypes, the profile of their metabolites analyzed by TLC, MS, and bioassay data. Then, genome shuffling was subsequently carried out with eight mutant strains, with two representatives from each protoplast mutant group, and genome shuffling mutant strains were obtained and screened using the same screening procedure. Although taxol has not been detected in any mutant, two important mutants, M-741 and G-444 were selected for metabolites isolation and determination due to their phenotypes, and differences in TLC analysis result from TF5 and other mutants. Three new sesquiterpenoids, namely tuberculariols A-C (1-3), and a known dihydroisocoumarin (4) were obtained from M-741. Eighteen novel compounds were isolated from G-444, including five new sesquiterpenoids (5-9), two new dihydroisocoumarins (10, 11), one new tetralone (12), together with 10 known compounds (13-20, 1, and 2). The compounds isolated from the M-741 and G-444 were different in structure types and substitutions from those of TF5 (15, 21-29). The results showed, for the first time, that protoplast mutations and genome shuffling are efficient approaches to mining natural products from endophytic fungi. Understanding the mechanisms of unlocking the biosynthesis of new metabolites will facilitate the manipulation of the secondary metabolism in fungi.

Marine fungi have proved to be rich sources of bioactive secondary metabolites [1][2][3][4]. During our systematic screening for bioactive compounds from marine-derived fungi, the strain of Penicillium sp. (M207142) was regarded as having one of the highest potentials among 174 strains isolated from sea sediment. The main active components of the strain are in the ethyl acetate extracts [5]. The extracts were subjected to a succession of chromatographic procedures to afford six pure components, the structures of which were established by spectral methods (IR, ESI-MS, and 1D and 2D NMR).Compound 1 ((2E,4E)-1-(2,6-dihydroxy-3,5-dimethyl-phenyl)hexa-2,4-dien-1-one)), yellow needle-like crystal, easily soluble in methanol. main correlation between the protons and carbons shown in Fig. 1. Compound 2, colorless solid, easily soluble in chloroform. IR (KBr, Q max , cm -1 ): 3440.72, 2925.81, 2855.30, 1722.32, 1598.51, 1383.93, 1025.13. The ESI-MS spectrum showed a molecular ion peak at m/z 251.2 [M+1] corresponding to the molecular formula C 14 H 18 O 4 , with molecular weight 250.2. Furthermore, the structure of compound 2 was confirmed by PMR, 13 C NMR, DEPT, COSY, HSQC, and HMBC experiments (Table 2), which is consistent with the structure of penicillone A [6]. Compound 3, colorless solid, IR (KBr, Q max , cm -1 ): 3355.81, 2926.10, 1625.97, 1383.45, 1158.12, 1026.36. ESI-MS spectrum of compound 3 showed a molecular ion peak at m/z 235.3 [M+1] + , with molecular weight 234.3 corresponding to the molecular formula C 14 H 18 O 3 . 1D and 2D NMR spectrum showed that the structure of compound 3 was consistent with the known compound dihydrosorbicillin [7].Compounds 4 to 6 were identified as 4-methoxybenzoic acid (4), 4-hydroxyphenylacetic acid (5), and methyl-4hydroxybenzoate (6). All of them are important chemical products used widely in industry.Compounds 1 and 3 exhibited potent cytotoxicity (IC 50 11.2 PM and 104.2 PM) against Hela cell line. Compounds 1 and 2 also showed potent cytotoxity against SW620 cell line, with inhibition 74 and 44% and tested concentration 10 Pg/mL.The cytotoxic values demonstrate the strong potential of compound 1 as a promising lead compound and the strain of Penicillium sp. (M207142) as a promising fungi source of new agents for cancer chemotherapy.

TF5. -Eight new metabolites, including new sesquiterpenoids (I), a new backbone sesquiterpene rearranged from guaiane, two disecoguaianes (II), two new dihydroisocoumarins (IV), and one new tetralone (III) are isolated together with ten known compounds. None of the new compounds shows antimicrobial activities. -(LU, C.-H.; LIU, S.-S.; WANG, J.-Y.; WANG, M.-Z.; SHEN*, Y.-M.; Helv. Chim. Acta 97 (2014) 3, 334-344, http://dx.