Open AccessBiotechnological production of the angiotensin‐converting enzyme inhibitory dipeptide isoleucine‐tryptophan
Author(s) -
Michelke Lydia,
Deussen Andreas,
Kettner Karina,
Dieterich Peter,
Hagemann Diana,
Kriegel Thomas M.,
Martin Melanie
Publication year - 2018
Publication title -
engineering in life sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.547
H-Index - 57
eISSN - 1618-2863
pISSN - 1618-0240
DOI - 10.1002/elsc.201700172
Subject(s) - dipeptide , inhibitory postsynaptic potential , tryptophan , enzyme , chemistry , angiotensin converting enzyme , isoleucine , biochemistry , amino acid , biology , endocrinology , leucine , blood pressure
Peptides with angiotensin‐converting enzyme (ACE)‐inhibitory and antihypertensive effects are suggested as innovative food additives to prevent or treat hypertension. Currently, these substances are isolated from food proteins following nonselective hydrolysis as a mixture of ACE‐inhibitory peptides and other protein fragments. This study presents an innovative biotechnological method, based on recombinant DNA technology that was established to specifically produce the ACE‐inhibitory dipeptide isoleucine‐tryptophan. In a first step, a repetitive isoleucine‐tryptophan construct fused to the maltose‐binding protein was generated and expressed in Escherichia coli BL21 cells. The chromatographically purified recombinant fusion protein was enzymatically hydrolyzed using α‐chymotrypsin to liberate the dipeptide isoleucine‐tryptophan. The identity of the liberated isoleucine‐tryptophan was confirmed by MS and derivatization of its N‐terminus. The ACE‐inhibitory effect of the recombinant dipeptide on soluble and membrane bound ACE was found to be indistinguishable from the inhibitory potential of the chemically produced commercially available dipeptide. The established experimental strategy represents a promising approach to the biotechnical production of sufficient amounts of recombinant peptide‐based ACE‐inhibitory and antihypertensive substances that are applicable as functional food additives to delay or even prevent hypertension.