Propeptin, a New Inhibitor of Prolyl Endopeptidase Produced by Microbispora. I. Fermentation, Isolation and Biological Properties.

Kimura, Ken‐ichi; Kanou, Fumiko; Takahashi, Hidetoshi; Esumi, Yasuaki; Uramoto, Masakazu; Yoshihama, Makoto

doi:10.7164/antibiotics.50.373

Cited by 72 publications

(79 citation statements)

References 28 publications

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“…They form three classes depending on the absence (class II) or presence of one (class III) or two (class I) disulfide bridges that further stabilize the structure [6]. They exhibit a variety of biological activities, involving enzyme inhibition, receptor antagonism, antimicrobial or anti-HIV activities (see Table 1 for class II lasso peptides) [5,[7][8][9][10][11][12]. Their compact structure confers to lasso peptides a great resistance to denaturing conditions and certain proteases.…”

Section: Introductionmentioning

confidence: 99%

Topoisomer Differentiation of Molecular Knots by FTICR MS: Lessons from Class II Lasso Peptides

Zirah

Afonso

Linne

et al. 2011

J. Am. Soc. Mass Spectrom.

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Lasso peptides constitute a class of bioactive peptides sharing a knotted structure where the C-terminal tail of the peptide is threaded through and trapped within an N-terminal macrolactam ring. The structural characterization of lasso structures and differentiation from their unthreaded topoisomers is not trivial and generally requires the use of complementary biochemical and spectroscopic methods. Here we investigated two antimicrobial peptides belonging to the class II lasso peptide family and their corresponding unthreaded topoisomers: microcin J25 (MccJ25), which is known to yield two-peptide product ions specific of the lasso structure under collisioninduced dissociation (CID), and capistruin, for which CID does not permit to unambiguously assign the lasso structure. The two pairs of topoisomers were analyzed by electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI-FTICR MS) upon CID, infrared multiple photon dissociation (IRMPD), and electron capture dissociation (ECD). CID and ECD spectra clearly permitted to differentiate MccJ25 from its non-lasso topoisomer MccJ25-Icm, while for capistruin, only ECD was informative and showed different extent of hydrogen migration (formation of c•/z from c/z • ) for the threaded and unthreaded topoisomers. The ECD spectra of the triply-chargedMccJ25 and MccJ25-lcm showed a series of radical b-type product ions ðb 0 I n Þ. We proposed that these ions are specific of cyclic-branched peptides and result from a dual c/z • and y/b dissociation, in the ring and in the tail, respectively. This work shows the potentiality of ECD for structural characterization of peptide topoisomers, as well as the effect of conformation on hydrogen migration subsequent to electron capture.

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Section: Introductionmentioning

confidence: 99%

Topoisomer Differentiation of Molecular Knots by FTICR MS: Lessons from Class II Lasso Peptides

Zirah

Afonso

Linne

et al. 2011

J. Am. Soc. Mass Spectrom.

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“…nonnitritogenes (IFO14045) and Microbispora indica (IFO14879), but not by Microbispora parva (IFO14043) [8]. Propeptin competitively inhibits the enzyme activity of prolyl endopeptidase (Kiϭ0.7 m M) and also has antimicrobial activity against Mycobacterium phlei IFO3158 (Inhibition zoneϭ12ϳ15 mm at 40 mg/disc) [6,9]. Peptide compounds similar to propeptin have been reported, including anantins (Gly-Asp type) [10,11], RES-701s (Gly-Asp type)…”

mentioning

confidence: 99%

“…1(a)) is an atypical cyclic peptide compound that has an amide bond between the a -amino group of the amino-terminal Gly1 and the b -carboxyl group of Asp9, and consists of 16 L configuration amino acids and 3 glycines [6,7]. It is produced by some Microbispora spp., such as Microbispora rosea (IFO14044), Microbispora rosea subsp.…”

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confidence: 99%

“…Seed culture (500 ml) prepared as described above (former seed culture was 140 ml to 18 liters [6]), was transferred into 18 liters of the same medium in a 30-liter jar fermenter. Fermentation was carried out at 28°C for 9 days (pH 7.8) and mycelia were obtained by filter press.…”

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confidence: 99%

“…Fermentation was carried out at 28°C for 9 days (pH 7.8) and mycelia were obtained by filter press. Isolation of propeptin and propeptin-2 was performed according to published methods [6], except that acetone was used for mycelium extraction and we used an additional BuOH extraction. Propeptin (584.4 mg) and propeptin-2 (114.6 mg) were isolated from the 36 liters of broth as brownish white powders.…”

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confidence: 99%

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Novel Propeptin Analog, Propeptin-2, Missing Two Amino Acid Residues from the Propeptin C-Terminus Loses Antibiotic Potency

et al. 2007

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A novel inhibitor of prolyl endopeptidase, the propeptin analog propeptin-2 (C 105 H 130 N 24 O 24 ), missing two amino acid residues from the propeptin C-terminus was isolated from the fermentation broth of propeptinproducing Microbispora sp. SNA-115 grown using a large inoculum. It shows the same enzyme inhibition activity as propeptin against prolyl endopeptidase (Kiϭ1.5 m M), but its antimicrobial activity against Mycobacterium phlei is more than 100-fold lower.Keywords propeptin, Microbispora sp., Mycobacterium spp., prolyl endopeptidase Prolyl endopeptidase (PEP; post-proline cleaving enzyme; official name: prolyl oligopeptidase; EC 3.4.21.26) cleaves peptide bonds at the carboxyl side of proline residues and hydrolyzes biologically active peptides containing proline, such as vasopressin and substance P [1,2]. It may also be involved in diseases such as Alzheimer's disease and bipolar affective disorder [3ϳ5]. Meanwhile, effective antituberculosis drugs with novel structures and mechanisms of action have not been developed in over 30 years. Moreover, the increase in Human Immunodeficiency Virus (HIV) and cancer patients has resulted in the spread of opportunistic bacteria, such as the Mycobacterium avium complex (MAC).Propeptin ( Fig. 1(a)

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Xanthomonine I–III: eine neue Klasse von Lassopeptiden mit einem Makrolactamring aus sieben Aminosäureresten

et al. 2014

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Lassopeptide gehçren zu den ribosomal synthetisierten und posttranslatorisch modifizierten Peptiden. Ihr gemeinsames Erkennungsmerkmal ist ein N-terminaler Makrolactamring, der von einem C-terminalen Schwanz durchfädelt wird. Diese "Lassofaltung" wird durch sterische Wechselwirkungen aufrechterhalten. In dieser Studie werden die Isolierung und Charakterisierung der Xanthomonine I-III, der ersten Lassopeptide mit einem nur aus sieben Aminosäuren bestehenden Makrolactamring, sowie die Kristallstruktur von Xanthomonin I und die NMR-spektroskopisch ermittelte Struktur von Xanthomonin II beschrieben. Insgesamt wurden 25 Xanthomonin-II-Varianten generiert, um Aspekte der Biosynthese, der Stabilisierung und der Aufrechterhaltug der Lassofaltung zu testen. Diese Mutagenesestudie offenbart die Einschränkungen, die ein so kleiner Ring für das Durchfädeln bedeutet, und zeigt, dass jede Stçpselaminosäure grçßer als Serin eine hitzestabile Lassofaltung in Xanthomonin II aufrechterhalten kann.Lassopeptide sind eine faszinierende Gruppe von Naturstoffen, die das einzigartige Strukturmotiv des Lassoknotens aufweisen. Dieses Strukturmerkmal besteht aus einem Makrolactamring, der zwischen der N-terminalen a-Aminogruppe und der Carbonsäureseitenkette eines Asp-oder GluRests gebildet wird und durch den der C-terminale Schwanz gefädelt ist, welcher durch Aminosäuren mit sterisch anspruchsvollen Seitenketten in Position gehalten wird. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] Diese Aminosäuren, sogenannte Stçpsel, sind über und unter dem Ring positioniert. Aufgrund ihrer Struktur sind Lassopeptide oft gegenüber proteolytischer und chemischer Degradation sowie in manchen Fällen auch thermisch außerge-wçhnlich stabil. [1,3,8,10,14,[16][17][18][19][20][21][22][23] Sie sind aber nicht nur wegen ihrer beispiellosen Faltung und ihrer nichtkovalenten Formstabilisierung von Interesse, sondern auch oft mit interessanten biologischen Eigenschaften verbunden, die von antimikrobiellen [3,10,11,18,20,24,25] über rezeptorantagonistischen [26][27][28] zu inhibitorischen Wirkungen [1,20,24,25,[29][30][31][32] reichen. Da ihre Biosynthesemaschinerie hochpromiskuitiv ist, kçnnen die meisten Reste in ihrer Sequenz mühelos ausgetauscht werden, was ihre erfolgreiche Nutzung zum Aufpropfen von Peptidepitopen mçglich machte.

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Propeptin, a New Inhibitor of Prolyl Endopeptidase Produced by Microbispora. I. Fermentation, Isolation and Biological Properties.

Cited by 72 publications

References 28 publications

Topoisomer Differentiation of Molecular Knots by FTICR MS: Lessons from Class II Lasso Peptides

Topoisomer Differentiation of Molecular Knots by FTICR MS: Lessons from Class II Lasso Peptides

Novel Propeptin Analog, Propeptin-2, Missing Two Amino Acid Residues from the Propeptin C-Terminus Loses Antibiotic Potency

Xanthomonine I–III: eine neue Klasse von Lassopeptiden mit einem Makrolactamring aus sieben Aminosäureresten

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