Tandem Mass Spectrum Similarity-Based Network Analysis Using C-13-Labeled And Non-Labeled Metabolome Data To Identify The Biosynthetic Pathway Of The Blood Pressure-Lowering Asparagus Metabolite Asparaptine A

The biosynthetic pathway of asparaptine, a naturally occurring inhibitor of angiotensin-converting enzyme (ACE) in vitro, is largely unknown in Asparagus officinalis. To determine which metabolites are involved in the pathway, we performed tandem mass spectrum similarity-based metabolome network analysis using C-13-labeled and non-labeled valine-fed asparagus calluses. We revealed that S-(2-carboxy-n-propyl)-cysteine as an intermediate and two new metabolites as asparaptine analogues, lysine- and histidine-type conjugates, are involved in the pathway. Asparaptine was therefore renamed asparaptine A (arginine type), and the two analogues were named asparaptines B (lysine type) and C (histidine type). Oral feeding of asparaptine A to a hypertensive mouse breed showed that this metabolite lowers both the blood pressure and heart rate within 2 h and the effect of asparaptine A wears off after 2 days. These results suggest that asparaptine A may not only have effects as an ACE inhibitor but also have beta-antagonistic effects.