Quinoxapeptins: Novel Chromodepsipeptide Inhibitors of HIV-1 and HIV-2 Reverse Transcriptase. I. The Producing Organism and Biological Activity.

Abstract

QuinoxapeptmA and B are novel chromodepsipeptides which were isolated from a nocardioform actinomycete with indeterminant morphology. Quinoxapeptins A and B are potent inhibitors of HIV-1and HIV-2reverse transcriptase and almost equally active against two single mutants forms as well as a double mutant form of HIV-1 reverse transcriptase. Qumoxapeptin A and B are specific inhibitors of HIV-1 and HIV-2 reverse transcriptase because they did not inhibit human DNA polymerase a, /?, y and S. Quinoxapeptin A and B are structurally similar to luzopeptin A which was also active against HIV-landHIV-2reverse transcriptase.

Biosynthetic Modularity Rules in the Bisintercalator Family of Antitumor Compounds

“…Five different genera ( Actinomadura , Micromonospora , Nocardioides , Streptomyces , Streptoverticillium and another unclassified actinomycete isolated from the bark of a birch Betula species) have been described as producers, which belong to four distant families ( Thermomonosporaceae , Micromonosporaceae , Nocardioidaceae and Streptomycetaceae ) [17,18,19,20,21,22]. This taxonomical diversity and the fact that these producer microorganisms were obtained from seas and lands of Africa, Asia and America continents, as well as that four different compounds were isolated just in strains collected in a single country (Japan) (Table 1) implies that probably new producers exist in different ecosystems all over the planet, just waiting for someone to discover them.…”

“…These two tailoring enzymes generate the corresponding 6-methoxy-3HQA and 6-methoxy-QXCA derivatives, found in luzopeptin and quinoxapeptin, respectively (Table 2, Scheme 2) [22,23]. With respect to amino acids core composition, all bisintercalators, as it has been described above, are composed of a short linear non-ribosomal peptide bound to the chromophore.…”

“…In luzopeptin B, the 4-hydroxy group at one 4-OH-Δ-piperazic acid residue is acetylated, whereas in luzopeptin A both 4-hydroxyl groups are acetylated [17,32]. The equivalent 4-OH-hydroxyl groups of quinoxapeptin A are also tailored with 2-methyl-cyclopropane carboxylic acids, whereas in quinoxapeptin B one of them contains acetate instead [22,33]. …”

“…This prevents these molecules from passing through their outer membrane [20]. For some members, inhibition of some cellular or viral specific enzymes has been also described [22]. …”

A new 16-membered tetraene macrolide JBIR-100 from a newly identified Streptomyces species

“…antitumor [368][369][370] , tuberculostatics [371] , anti-inflammatory [372] and anti-HIV agents [373,374] . Monamycin, a series of antibiotics [16] , containing piperazic acids have been isolated from the culture broth of numerous Streptomyces spp.…”