https://pubs.rsc.org/en/content/articlepdf/2019/NP/C8NP00092A

Marine natural products.

Induction of cell death and inhibition of cell survival are the main principles of cancer therapy. Resistance to chemotherapeutic agents is a major problem in oncology, which limits the effectiveness of anticancer drugs. A variety of factors contribute to drug resistance, including host factors, specific genetic or epigenetic alterations in the cancer cells and so on. Although various mechanisms by which cancer cells become resistant to anticancer drugs in the microenvironment have been well elucidated, how to circumvent this resistance to improve anticancer efficacy remains to be defined. Autophagy, an important homeostatic cellular recycling mechanism, is now emerging as a crucial player in response to metabolic and therapeutic stresses, which attempts to maintain/restore metabolic homeostasis through the catabolic lysis of excessive or unnecessary proteins and injured or aged organelles. Recently, several studies have shown that autophagy constitutes a potential target for cancer therapy and the induction of autophagy in response to therapeutics can be viewed as having a prodeath or a prosurvival role, which contributes to the anticancer efficacy of these drugs as well as drug resistance. Thus, understanding the novel function of autophagy may allow us to develop a promising therapeutic strategy to enhance the effects of chemotherapy and improve clinical outcomes in the treatment of cancer patients.

/pdf/autophagy-and-chemotherapy-resistance-a-promising-2pz6sno24p.pdf

Autophagy and chemotherapy resistance: a promising therapeutic target for cancer treatment

https://orbit.dtu.dk/files/101320049/elsevier_4_.pdf

Identification and nomenclature of the genus Penicillium.

New developments in RiPP discovery, enzymology and engineering

Marine-derived bacteria and fungi are promising sources of novel bioactive compounds that are important for drug discovery programs. However, as encountered in terrestrial microorganisms there is a high rate of redundancy that results in the frequent re-discovery of known compounds. Apparently only a part of the biosynthetic genes that are harbored by fungi and bacteria are transcribed under routine laboratory conditions which involve cultivation of axenic microbial strains. Many biosynthetic genes remain silent and are not expressed in vitro thereby seriously limiting the chemical diversity of microbial compounds that can be obtained through fermentation. In contrast to this, co-cultivation (also called mixed fermentation) of two or more different microorganisms tries to mimic the ecological situation where microorganisms always co-exist within complex microbial communities. The competition or antagonism experienced during co-cultivation is shown to lead to a significantly enhanced production of constitutively present compounds and/or to an accumulation of cryptic compounds that are not detected in axenic cultures of the producing strain. This review highlights the power of co-cultivation for increasing the chemical diversity of bacteria and fungi drawing on published studies from the marine and from the terrestrial habitat alike.

https://www.mdpi.com/1660-3397/12/2/1043/pdf

Co-Cultivation—A Powerful Emerging Tool for Enhancing the Chemical Diversity of Microorganisms

Eight new a-pyrone derivatives, namely, nigerapyrones A-E (1-5) and nigerapyrones F-H (8-10), along with two known congeners, asnipyrones B (6) and A (7), were isolated from Aspergillus niger MA-132, an endophytic fungus obtained from the fresh tissue of the marine mangrove plant Avicennia marina. The structures of these compounds were elucidated on the basis of spectroscopic analysis. The undescribed geometries of the trisubstituted double bonds (C-9 and C-11) for asnipyrone B (6) have now been explicitly determined, while the incorrect placement of the methyl group at C-5 of asnipyrone A (7) has now been revised at C-3. The cytotoxic activities of the isolated a-pyrone derivatives against eight tumor cell lines as well as antimicrobial activities against two bacteria and four plant-pathogenic fungi of these compounds were evaluated. Compounds 2, 4, 5, and 7 showed weak cytotoxicity against some of the tested tumor cell lines.

Nigerapyrones A-H, α-pyrone derivatives from the marine mangrove-derived endophytic fungus Aspergillus niger MA-132.

Cristatumins A-D, new indole alkaloids from the marine-derived endophytic fungus Eurotium cristatum EN-220.

Bioassay-guided isolation of a fungal strain Nigrospora sp. MA75, an endophytic fungus obtained from the marine semi-mangrove plant Pongamia pinnata, which was fermented on three different culture media, resulted in the isolation and identification of seven known compounds, 2, 3, and 59, from a medium containing 3.5% NaCl, while a new compound, 2,3-didehydro-19a-hydroxy-14-epicochlioquinone B (10) was obtained from the medium containing 3.5% NaI. In addition, two new griseofulvin derivatives, 6-O-desmethyldechlorogriseofulvin (1) and 6'-hydroxygriseofulvin (4), were isolated and identified from the rice solid medium. Dechlorogriseofulvin (2) and griseofulvin (3) were the major components in fermentation extracts of all these culture media, while compounds 1 and 4, 5 and 6, and 10 were only present in the extract of respective culture medium. The structures of these compounds were elucidated by detailed spectroscopic analysis, and the absolute configuration of 1 was determined by CD measurement. Compounds 9 and 10 exhibited antibacterial activities toward five tested bacterial strains, while compounds 5, 6, and 8 selectively inhibited MRSA, E. coli, and S. epidermidis, and compound 3 showed moderate activity against V. mali and S. solani. Moreover, compound 10 potently inhibited the growth of MCF-7, SW1990, and SMMC7721 tumor cell lines with IC50 values of 4, 5, and 7 mu g/ml, respectively.

Diverse secondary metabolites produced by marine-derived fungus Nigrospora sp. MA75 on various culture media.

Penicillium sp. MA-37, which was obtained from the rhizospheric soil of the mangrove plant Bruguiera gymnorrhiza, exhibited different chemical profiles in static and shaken fermentation modes. Three new meroterpenoid derivatives, 4,25-dehydrominiolutelide B (1), 4,25-dehydro-22-deoxyminiolutelide B (2), and isominiolutelide A (3), together with three known ones were characterized from its static fermentation, while three new diphenyl ether derivatives, namely, Delta(1',3')-1'-dehydroxypenicillide (4), 7-O-acetylsecopenicillide C (5), and hydroxytenellic acid B (6), along with five related metabolites were isolated from the shaken culture. The structures of these compounds were elucidated on the basis of spectroscopic analysis, and the structure of compound 2 was confirmed by X-ray crystallographic analysis. The absolute configurations of 1-3 and 6 were determined by ECD and modified Mosher's method, respectively. All isolated compounds were evaluated for brine shrimp lethality and antibacterial activity.

Meroterpenoid and Diphenyl Ether Derivatives from Penicillium sp. MA-37, a Fungus Isolated from Marine Mangrove Rhizospheric Soil

Bioassay-guided fractionation of the crude extract from Penicillium commune SD-118, a fungus obtained from a deep-sea sediment sample, resulted in the isolation of a known antibacterial compound, xanthocillin X (1), and 14 other known compounds comprising three steroids (2–4), two ceramides (5 and 6), six aromatic compounds (7–12), and three alkaloids (13–15). Xanthocillin X (1) was isolated for the first time from a marine fungus. In the bioassay, xanthocillin X (1) displayed remarkable antimicrobial activity against Staphylococcus aureus and Escherichia coli, and significant cytotoxicity against MCF-7, HepG2, H460, Hela, Du145, and MDA-MB-231 cell lines. Meleagrin (15) exhibited cytotoxicity against HepG2, Hela, Du145, and MDA-MB-231 cell lines. This is the first report of the cytotoxicity of xanthocillin X (1).

Zhuo Shang

Papers

Nigerapyrones A-H, α-pyrone derivatives from the marine mangrove-derived endophytic fungus Aspergillus niger MA-132.

Cristatumins A-D, new indole alkaloids from the marine-derived endophytic fungus Eurotium cristatum EN-220.

Diverse secondary metabolites produced by marine-derived fungus Nigrospora sp. MA75 on various culture media.

Meroterpenoid and Diphenyl Ether Derivatives from Penicillium sp. MA-37, a Fungus Isolated from Marine Mangrove Rhizospheric Soil

Chemical profile of the secondary metabolites produced by a deep-sea sediment-derived fungus Penicillium commune SD-118