Next Article in Journal
Temporal Effects on Radiation Responses in Nonhuman Primates: Identification of Biofluid Small Molecule Signatures by Gas Chromatography–Mass Spectrometry Metabolomics
Previous Article in Journal
Inhibitory Effects of Green Tea Polyphenols on Microbial Metabolism of Aromatic Amino Acids in Humans Revealed by Metabolomic Analysis
Article Menu

Export Article

Open AccessArticle

The Health Promoting Bioactivities of Lactuca sativa can be Enhanced by Genetic Modulation of Plant Secondary Metabolites

Department of Biochemistry, Quaid-I-Azam University, 45320 Islamabad, Pakistan
Institute for Global Food Security, School of Biological Sciences, Queen’s University Belfast, Biological Sciences Building, Chlorine Gardens, Belfast BT9 5DL, UK
Core Technology Unit for Mass Spectrometry, Faculty of Medicine, Health and Life Sciences, Queen’s University Belfast, Belfast BT9 5DL, UK
Author to whom correspondence should be addressed.
Current affiliation: Department of Biochemistry and Biotechnology, University of Gujrat, 50700 Gujrat, Pakistan.
Metabolites 2019, 9(5), 97;
Received: 5 April 2019 / Revised: 28 April 2019 / Accepted: 1 May 2019 / Published: 12 May 2019
PDF [1498 KB, uploaded 12 May 2019]


Plant secondary metabolites are protective dietary constituents and rol genes evidently increase the synthesis of these versatile phytochemicals. This study subjected a globally important vegetable, lettuce (Lactuca sativa) to a combination of untargeted metabolomics (LC-QTof-MS) and in vitro bioactivity assays. Specifically, we examined the differences between untransformed cultured lettuce (UnT), lettuce transformed with either rolABC (RA) or rolC (RC) and commercially grown (COM) lettuce. Of the 5333 metabolite features aligned, deconvoluted and quantified 3637, 1792 and 3737 significantly differed in RA, RC and COM, respectively, compared with UnT. In all cases the number of downregulated metabolites exceeded the number increased. In vitro bioactivity assays showed that RA and RC (but not COM) significantly improved the ability of L. sativa to inhibit α-glucosidase, inhibit dipeptidyl peptidase-4 (DPP-4) and stimulate GLP-1 secretion. We putatively identified 76 lettuce metabolites (sesquiterpene lactones, non-phenolic and phenolic compounds) some of which were altered by several thousand percent in RA and RC. Ferulic acid levels increased 3033–9777%, aminooxononanoic acid increased 1141–1803% and 2,3,5,4′tetrahydroxystilbene-2-O-β-d-glucoside increased 40,272–48,008%. Compound activities were confirmed using commercially obtained standards. In conclusion, rol gene transformation significantly alters the metabolome of L.sativa and enhances its antidiabetic properties. There is considerable potential to exploit rol genes to modulate secondary metabolite production for the development of novel functional foods. This investigation serves as a new paradigm whereby genetic manipulation, metabolomic analysis and bioactivity techniques can be combined to enable the discovery of novel natural bioactives and determine the functional significance of plant metabolites.
Keywords: Lettuce; plants; secondary metabolites; metabolomics; diabetes Lettuce; plants; secondary metabolites; metabolomics; diabetes
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Supplementary material


Share & Cite This Article

MDPI and ACS Style

Ismail, H.; Gillespie, A.L.; Calderwood, D.; Iqbal, H.; Gallagher, C.; Chevallier, O.P.; Elliott, C.T.; Pan, X.; Mirza, B.; Green, B.D. The Health Promoting Bioactivities of Lactuca sativa can be Enhanced by Genetic Modulation of Plant Secondary Metabolites. Metabolites 2019, 9, 97.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
Metabolites EISSN 2218-1989 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top