Kenalactams A–E, Polyene Macrolactams Isolated from Nocardiopsis CG3

Abstract

Actinobacteria are one of the most important phyla of microorganisms that produce a wide variety of bioactive secondary metabolites, 1,2 including many clinically used antibiotics and anticancer drugs. 3,4 A contemporary strategy for obtaining new bioactive compounds is based on the isolation of rare actinomycetes from neglected environments, 5 which should contain gene clusters for biosynthetizing novel secondary metabolites. 6 One of the pharmaceutically and biotechnologically important rare actinomycetes that attracts natural products researchers is the genus Nocardiopsis. 7,8 Species of this genus are aerobic, Gram-positive, non-acid-fast, and their aerial mycelia bear long chains of spores. 9,10 Nocardiopsis species were mainly recovered from salty habitats. The members of this genus produce an array of bioactive compounds that may aid their survival under these conditions. 11 In recent years many new natural products, belonging to different classes of molecules, including polyketides and peptides, 12,13,14 were isolated from Nocardiopsis species. 15,16 These classes display cytotoxic, 17 antimicrobial, 18 and immunomodulatory activities. 19 Recently, three new angucyclines, nocardiopsistins A-C, with anti-Methicillin-Resistant Staphylococcus aureus (MRSA) activity were isolated from a marine sponge-derived Nocardiopsis sp. HB-J378, 20 and a new cytotoxic cyclic peptide was obtained from the marine sponge-associated Nocardiopsis sp. UR67. 14 According to the World Health Organization (WHO, 2018), «Cancer is the second leading cause of death globally, and is responsible for an estimated 9.6 million deaths in 2018 », hence it is necessary to continue the discovery of new classes of molecules with cytotoxic activity, which may be further developed as anticancer drugs. 14 In fact, cytotoxicity-guided fractionation of the crude extract of the marine obligate actinomycetes, Salinispora tropica, led to the isolation of salinosporamide A, which entered phase I human clinical trials for the treatment of multiple myeloma. 21 In the course of screening for new bioactive metabolites from our collection of actinobacteria, which had been isolated from different areas of Algeria, Nocardiopsis CG3

Insights into the Variation in Bioactivities of Closely Related Streptomyces Strains from Marine Sediments of the Visayan Sea against ESKAPE and Ovarian Cancer

“…The strategy of using marine microorganisms as a source of new therapeutic agents is not unfeasible as it has been the focus of many recent investigations in other countries [ 5 , 13 , 20 , 40 , 41 , 42 , 43 , 44 , 45 ] and has led to the discovery of bioactive compounds with unique chemical entities. These include antitubercular sporalactam A and B [ 46 ] and dumulmycin [ 47 ], anticancer nahuoic acids [ 48 , 49 ] and kenalactams [ 50 ], and antibiotics bisanhydroaklavinone and 1-hydroxyaklavinone [ 11 ]. The conditions in the marine environment are extremely different from that of the terrestrial habitat: it is very demanding, nutrient deficient, competitive, and hostile and is inundated with high salinity and high pressure [ 18 , 38 , 39 , 51 ].…”

Selective isolation, antimicrobial screening and phylogenetic diversity of marine actinomycetes derived from the Coast of Bejaia City (Algeria), a polluted and microbiologically unexplored environment

“…This isolate can thus be considered a presumptive new Streptomyces species. Moreover, several studies in Algeria have recorded the Nocardiopsis genera from soil samples, such as the desert soil (Meklat et al, 2011; Zitouni et al, 2005), the salt pan of the Kenadsa region (located in southwest Algeria) (Messaoudi et al, 2019), a salt lake in the Algerian Sahara (Hadj Rabia‐Boukhalfa et al, 2017), and from the rhizosphere‐associated with semi‐arid soil in the North‐East of Algeria (Aouar et al, 2012). However, Nocardiopsis strains had never been isolated from marine environments in Algeria.…”

Polyene Macrolactams from Marine and Terrestrial Sources: Structure, Production Strategies, Biosynthesis and Bioactivities

“…To confirm the beginning unit of the amino acid involved in the biosynthesis route of kenalactam A (2), 11 amino acids were added separately into the medium, and then the products were characterized using the LC-MS technique by Omar Messaoudi et al ( 2018). As a consequence, L-alanine is likely to be the first unit in the structure of kenalactam A [20] because the amide groups in kenalactam A are separated by one carbon from the methyl branched chain at C24, which may mean that 3-methyl aspartic acid is the starting unit of amino acid for biosynthesis.…”