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Covering: 2009 to 2015Lignans and neolignans are a large group of natural products derived from the oxidative coupling of two C6-C3 units. Owing to their biological activities ranging from antioxidant, antitumor, anti-inflammatory to antiviral properties, they have been used for a long time both in ethnic as well as in conventional medicine. This review describes 564 of the latest examples of naturally occurring lignans and neolignans, and their glycosides in some cases, which have been isolated between 2009 and 2015. It comprises the data reported in more than 200 peer-reviewed articles and covers their source, isolation, structure elucidation and bioactivities (where available), and highlights the biosynthesis and total synthesis of some important ones.

The pentacyclic quinoline alkaloid camptothecin (1) is a potent antineoplastic agent. Two of its analogues, 9-methoxycamptothecin (2) and 10-hydroxycamptothecin (3), exhibit similar potency but do not have the potential therapeutic drawbacks produced by unmodified 1. We have established methodology for the isolation and unequivocal identification and characterization of a novel endophytic fungus isolated from the inner bark of the medicinal plant Camptotheca acuminata, which produced 1-3 in rich mycological medium (Sabouraud dextrose broth), under shake-flask fermentation conditions. The fungus was identified by its morphology and authenticated by ITS analysis (ITS1 and ITS2 regions and the intervening 5.8S rDNA region). Camptothecin (1) and its analogues were identified by 1H NMR spectroscopy and LC-HRMS and confirmed by comparison with authentic standards. The production pattern of the metabolites over seven successive subculture generations of this endophyte was studied. A sharp attenuation in the production of 1 and 2 was observed from the first- through to the seventh-generation subculture. Therefore, these results offer a caution as to the possibility of using endophytic fungi as alternate sources of plant secondary metabolite production. Further studies have been initiated on the analysis of the upstream metabolic intermediates to understand the steps at which the production of the metabolites in question is constrained.

For the first time, an endophytic fungus has been isolated from the stems of the medicinal herb Hypericum perforatum (St. John's Wort). The fungus produced the napthodianthrone derivative hypericin ( 1) in rich mycological medium (potato dextrose broth) under shake flask and bench scale fermentation conditions. Emodin ( 2) was also produced simultaneously by the fungus under the same culture conditions. We propose 2 as the main precursor in the microbial metabolic pathway to 1. The fungus was identified by morphology and authenticated by 28S (LSU) rDNA sequencing. Compounds 1 and 2 were identified by LC-HRMS, LC-MS/MS, and LC-HRMS/MS and confirmed by comparison with authentic standards. In bioassays with a panel of laboratory standard pathogenic control strains, including fungi and bacteria, both fungal 1 and 2 possessed antimicrobial activity comparable to authentic standards. This endophytic fungus has significant scientific and industrial potential to meet the pharmaceutical demands for 1 in a cost-effective, easily accessible, and reproducible way.

Aims: Isolation, identification and characterization of an endophytic fungus from Juniperus communis L. Horstmann, as a novel producer of deoxypodophyllotoxin and its in vitro antimicrobial assay. Methods and Results:The methodology for the isolation, identification and characterization of a novel endophytic fungus from the twigs of the J. communis L. Horstmann plant, which specifically and consistently produces deoxypodophyllotoxin, was unequivocally established. The fungus was identified as Aspergillus fumigatus Fresenius by molecular, morphological and physiological methods. Deoxypodophyllotoxin was identified and quantified by high-resolution LC-MS, LC-MS 2 and LC-MS 3 . The antimicrobial efficacy of the fungal deoxypodophyllotoxin against a panel of pathogenic bacteria was established. Conclusions: The production of deoxypodophyllotoxin (found in the host) by the cultured endophyte is an enigmatic observation. It demonstrates the transfer of gene(s) for such accumulation by horizontal means from the host plant to its endophytic counterpart. It would be interesting to further study the deoxypodophyllotoxin production and regulation by the cultured endophyte in J. communis and in axenic cultures. Significance and Impact of the Study: This endophyte is a potential handle for scientific and commercial exploitation. Although the current accumulation of deoxypodophyllotoxin by the endophyte is not very high, it could be scaled-up to provide adequate production to satisfy new drug development and clinical needs. However, further refined precursor-feeding and mass-balance studies are required to result in the consistent and dependable production. 1019 podophyllotoxin biosynthesis are not precisely known. Therefore, an alternative to the synthesis and isolation from natural sources is production by biotechnological techniques starting from deoxypodophyllotoxin (Fig. 1b). It has been documented that deoxypodophyllotoxin can be converted into podophyllotoxin or 6-methoxypodophyllotoxin and their glycosides using plant cell cultures (Van Uden et al. 1997;Koulman et al. 2003). However, deoxypodophyllotoxin is not readily available from commercial sources because of its scarcity from natural sources and cumbersome extraction procedures. Hence, it is desirable to develop alternative sources for the production of the aryl tetralin lignan, deoxypodophyllotoxin, which might be used as a precursor to develop anticancer drugs and as a substrate for bioconversion studies.In addition to being a potential precursor of the antineoplastic moiety podophyllotoxin, deoxypodophyllotoxin itself is an important lignan that possesses therapeutic efficacy against a plethora of malignancies. Deoxypodophyllotoxin has been shown to demonstrate remarkable anticancer activities against a number of tumour cell lines including A549, SK-OV-3, SK-MEL-2, HCT15, B16F10 and K562 (Kim et al. 2002;Masuda et al. 2002). It is also active against Herpes simplex virus (Sudo et al. 1998) and has considerable antiproliferative effects (Ikeda et al. 19...

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Microorganisms are well-known producers of a wide variety of bioactive compounds that are utilized not only for their primary metabolism but also for other purposes such as defense, detoxification, or communication with other micro- and macro-organisms. Natural products containing a 'decalin ring' occur often in microorganisms. They exhibit diverse and remarkable biological activities, including antifungal, antibacterial, anticancer and immunosuppressive activities, to name a few. This review surveys the natural decalin-type compounds that have been isolated from microorganisms, with emphasis on both chemical and biological implications. Total syntheses of some important decalin moiety-containing natural products are also highlighted.