Strategies for recombinant production of antimicrobial peptides with pharmacological potential

ABSTRACT

Introduction

The need to develop new drugs for the control of pathogenic microorganisms has redoubled efforts to prospect for antimicrobial peptides (AMPs) from natural sources and to characterize its structure and function. These molecules present a broad spectrum of action against different microorganisms and frequently present promiscuous action, with anticancer and immunomodulatory activities. Furthermore, AMPs can be used as biopharmaceuticals in the treatment of hospital-acquired infections and other serious diseases with relevant social and economic impacts.Areas covered: The low yield and the therefore difficult extraction and purification process in AMPs are problems that limit their industrial application and scientific research. Thus, optimized heterologous expression systems were developed to significantly boost AMP yields, allow high efficiency in purification and structural optimization for the increase of therapeutic activity.Expert opinion: This review provides an update on recent developments in the recombinant production of ribosomal and non-ribosomal synthesis of AMPs and on strategies to increase the expression of genes encoding AMPs at the transcriptional and translational levels and regulation of the post-translational modifications. Moreover, there are detailed reports of AMPs that have already reached marketable status or are in the pipeline under advanced stages of preclinical testing.

KEYWORDS:

• Antimicrobial peptides
• antimicrobial resistance
• expression systems
• recombinant peptides
• heterologous expression
• recombinant peptides

Article highlights

• Increased microbial resistance against antibiotics due to natural processes such as intrinsic resistance, vertical or horizontal evolution, and frequent use associated with widespread and long-term applications.

• The challenge to develop alternative antimicrobial therapies that are more effective and less likely to select resistant strains.

• AMPs as a new strategy for the development of antimicrobial therapies.

• Heterologous production of ribosomal and non-ribosomal AMPs synthesized using different expression systems.

• The purification methods of recombinant AMPs and the importance of this step for the development of biopharmaceuticals.

• Different AMPs have already achieved clinical trials. However, difficulties in reaching market status are outlined here.

Declaration of interest

All of the authors have previously received funding from the Coordination of Improvement of Higher Education Personnel (CAPES); National Council of Technological and Scientific Development (CNPq), Federal District Research Support Foundation (FAPDF) and Support Foundation for the Development of Education, Science and Technology of the State of Mato Grosso do Sul (FUNDECT). The authors have no other affiliations or financial involvement with any other organization or entity that has any interest or financial conflict with the subject or materials discussed in the manuscript other than those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no other relevant financial interests or relationships to disclose.

Additional information

Funding

This work was supported by the Coordination of Improvement of Higher Education Personnel (CAPES); National Council of Technological and Scientific Development (CNPq), Federal District Research Support Foundation (FAPDF) and Support Foundation for the Development of Education, Science and Technology of the State of Mato Grosso do Sul (FUNDECT).