Microbial production of small peptide: pathway engineering and synthetic biology

Abstract

Small peptides are a group of natural products with low molecular weights and complex structures. The diverse structures of small peptides endow them with broad bioactivities and suggest their potential therapeutic use in the medical field. The remaining challenge is methods to address the main limitations, namely (i) the low amount of available small peptides from natural sources, and (ii) complex processes required for traditional chemical synthesis. Therefore, harnessing microbial cells as workhorse appears to be a promising approach to synthesize these bioactive peptides. As an emerging engineering technology, synthetic biology aims to create standard, well-characterized and controllable synthetic systems for the biosynthesis of natural products. In this review, we describe the recent developments in the microbial production of small peptides. More importantly, synthetic biology approaches are considered for the production of small peptides, with an emphasis on chassis cells, the evolution of biosynthetic pathways, strain improvements and fermentation.

Antimicrobial Peptides: An Update on Classifications and Databases

“…Similarly, improved molecular dynamics and deep learning algorithms can be developed to extract extensive features from already reported antimicrobial, non-antimicrobial, cytotoxic, and non-cytotoxic AMPs. The mining of halicin for resistant infections is a promising example of deep learning in the drug discovery and development pipline [ 616 ]. Similarly, the advent of alpha fold, which represents a significant breakthrough in computational biology, exemplifies the promise of deep learning approaches in AMPs discovery [ 540 ].…”

Production, Purification, and Potential Health Applications of Edible Seeds’ Bioactive Peptides: A Concise Review

“…This process includes the synthesis of peptides' coding region and consequent cloning through prokaryotic or eukaryotic expression vectors using E. coli or yeast as host cells. This cloning approach permits the construction and expression of more than one peptide concurrently [58]. For example, a recent work reported the successful simultaneous cloning and expression of ten ACE-inhibitory peptides (DKIHPF, YQQPVL, IPP, VPP, LKPNM, RPLKPW, KVLPVPE, SKVYPFPGPI, YLAHKALPMHIR, and FFVAPFPEVFGK) in rice grain [59].…”

Biocatalytic synthesis of peptidic natural products and related analogues

“…Compared with synthetic methods that have been developed and evolved for peptide synthesis for a long time, biocatalytic approaches are still in the early stage of industrial applications. Fortunately, the advances of synthetic biology (Wu et al, 2021b), DNA sequencing and synthesis technologies, and machinelearning-aided protein engineering (Wu et al, 2019) are opening unpreceded opportunities for discovery and development of biocatalysts for peptide synthesis in vitro and in vivo. Given rich biosynthetic toolkits available in nature and a growing understanding of PNP biosynthesis, biocatalytic synthesis of PNPs and analogues will become practical in the coming years.…”