Microginin FR1, a linear peptide from a water bloom of Microcystis species

Abstract

A so far unknown structural variant, called microginin FR1, of cyanobacterial peptides of the microginin type was isolated from a water bloom of a German lake. The bloom consisted almost exclusively of Microcystis sp. cells. The structure of microginin FR1 was identified by amino acid analysis, determination of the relative molecular mass by electrospray mass spectrometry, and by NMR to be a linear pentapeptide with a relative molecular mass of 727 which contains a β‐amino‐α‐hydroxy‐decanoic acid (Ahda), alanine, N‐methyl‐leucine, and two tyrosine units (Ahda‐Ala‐N‐Me‐Leu‐Tyr‐Tyr). Microginin FR1 had angiotensin‐converting enzyme inhibitory activity with half‐maximal inhibition at 6×10−5 M microginin FR1.

Binding structure of the leucine aminopeptidase inhibitor microginin FR1

“…The cyanobacterial peptide microginin FR1 represents a large group of known microginins characterized by the N‐terminal residue Ahda [9,10,27,28]. The IC 50 values of microginin FR1 for bovine lens cytosolic LAP (EC 3.4.11.1) was determined as 1.3 μM, which is lower than the value 16 μM for ACE [15]. The IC 50 values of the other microginins for ACE are in the range of 10 μM or above [9,16,28].…”

“…Both of them inhibit aminopeptidases [13]; bestatin causes a reduction of the HIV‐infection rate [14]. Here we report the binding structure of microginin FR1 that was extracted from a water bloom in a local lake [15] to a leucine aminopeptidase (LAP).…”

“…Covalent structure of the pentapeptide microginin FR1 with its characteristic Ahda residue [15]. The related dipeptide bestatin [11] and tetrapeptide amastatin [12] carry a modified Ahda as the first residue.…”

An angiotensin-converting enzyme-inhibitory metabolite with partial structure of microginin in a cyanobacterium Anabaena fertilissima CCC597, producing fibrinolytic protease

“…A pentapeptide termed microginin-FR1 (M r =728 Da) isolated from another strain of Microcystis sp. displayed identical amino acid sequence, though with an additional terminal Tyr (Neumann et al 1997). Microginins have been associated with the antibacterial properties of cyanobacteria (Silva-Stenico et al 2011).…”

Determination of the toxicity of the freshwater cyanobacterium Woronichinia naegeliana (Unger) Elenkin

“…Some of these oligopeptides have been recognized as leucine aminopeptidase (LAP) inhibitors due to the 2S configuration of the Ahda group (Ishida et al 1997; Neumann et al 1997). The structure N-Me-Tyr-Tyr at the C-terminus seemed to be crucial for the inhibition of angiotensin-converting enzyme (ACE) (Ishida et al 2000).…”