Protein and Peptide Letters - Volume 24, Issue 2, 2017

Natural, synthetic and analogues of peptides have shown prospects for application in cancer chemotherapy. Notably, some food protein-derived peptides are known to possess anticancer activities in cultured cancer cells, and also in animal cancer models via different mechanisms including induction of apoptosis, cell cycle arrest, cellular membrane disruption, inhibition of intracellular signalling, topoisomerases and proteases, and antiangiogenic activity. Although the mechanism of several anticancer food peptides is yet to be clearly elucidated, there is potential for practical applications of the peptides as functional food and nutraceutical ingredients, especially in adjuvant cancer therapy. This review describes the aetiological mechanisms of cancers and the production, structures, mechanisms of action, availability, and cellular and physiological anticancer activities of the food peptides.

There is a growing interest in the incorporation of functional foods in the daily diet to achieve health promotion and disease risk reduction. Numerous studies have focused on the production of biologically active peptides as nutraceuticals and functional food ingredients due to their health benefits. These short peptides, displaying antihypertensive, antioxidant, mineral binding, immunomodulatory and antimicrobial activities are hidden in a latent state within the primary sequences of food proteins requiring enzymatic proteolysis for their release. While microbial fermentation is one of the major and economically most convenient processes used to generate bioactive peptides, lactic acid bacteria (LAB) are widely used as starter cultures for the production of diverse fermented foods. This article reviews the current knowledge on LAB as cell factories for the production of bioactive peptides from a variety of food protein sources. These microorganisms depend on a complex proteolytic system to ensure successful fermentation processes. In the dairy industry, LAB containing cell envelope-associated proteinases (CEPs) are employed as biocatalysts for the first step of casein breakdown releasing bioactive peptides during milk fermentation. A better understanding of the functionality and regulation of the proteolytic system of LAB opens up future opportunities for the production of novel food-derived compounds with potential health-promoting properties.

Src is a non-receptor protein tyrosine kinase ubiquitously expressed in animals. It is involved in various cellular processes, including the innate immune response in mammals. However, less is known about the function of insect Src. Here we presented a homologue of Src in silkworm (Bombyx mori), named as BmSrc by phylogenetic analysis, homologous comparison and domain prediction. BmSrc contains the conserved phosphorylation residues and possesses tyrosine kinase activity. The expression pattern of BmSrc mRNA was specific in developmental stages and tissues. The highest expression of BmSrc was detected in moth stage, and the gonads showed the highest expression during larval stage. We then found over-expression of BmSrc in BmE cell resulted in an increase of p38 mitogen-activated protein kinase (p38 MAPK) and Akt phosphorylation but a decrease in extracellular signal–regulated kinase (ERK) phosphorylation. Finally, we demonstrated that BmSrc promoted the production of antimicrobial peptides (AMPs). These results implied that BmSrc is involved in immune response of silkworm possibly through activating p38 MAPK and Akt signaling pathway. Our study may provide reference for further investigation of the biological function of BmSrc in Bombyx mori.

Peptidoglycan (PG) is an essential component of the cell wall, and undergoes reconstruction by various PG hydrolases during cell growth, development and division. The murein- tripeptide (Mtp) amidase MpaA belongs to PG hydrolase family and is responsible for cleaving the γ-D-Glumeso- Dap amide bond in the Mtp released during PG turnover. The current paper reports the crystal structure of MpaA from Escherichia coli (E. coli) O157 at 2.6 Šresolution. The asymmetric unit consists of two protein molecules and each monomer represents the common α/β; fold of metallocarboxypeptidases (MCP). The Tyr133-Asp143 loop appears to mediate the entrance and binding of the substrate into the active groove. A structural comparison of MpaA with its homologue from Vibrio harveyi showed that MpaA has narrower active pocket entrance with a smaller surface opening, which is determined by the Val204-Thr211 loop. The reported structure provides a starting point for the molecular mechanism of MpaA in a significant human pathogen.