Engineering the Microbial Platform for the Production of Biologics and Small-Molecule Medicines, Volume II

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Background

Given the success of Volume I of this Research Topic, and the rapidly evolving subject area, we are pleased to announce the launch of Volume II: Engineering the Microbial Platform for the Productions of Biologics and Small-Molecule Medicines.

Natural products (NP) are the matchless starting point for drug discovery, because the major antimicrobials or chemotherapeutics entering clinical trials are based on them. Generally, drugs belonging to natural origin can be produced from primary/secondary metabolism of different micro-organisms. They can be broadly classified as (i) native NPs, (ii) derivatives of NPs or (iii) synthetic products based on structures of NPs. NPs exhibit a wide range of pharmacophores and a high degree of stereochemistry, whereas native or derived NPs are superior to completely synthesized counterparts due to property of “metabolite-likeness”. These host micro-organisms that are otherwise termed as “microbial cell factories” due to their ability of acting as miniature factories for production of targeted compounds. The recent developments of high-throughput techniques for deciphering genomes, transcriptomes, proteomes, metabolomes and fluxomes, together with computational and bioinformatics tools have assisted in system-level metabolic engineering approaches for those bio-factories.

In some case the useful NPs are not amenable to be produced at significant level or cryptic in native host or the hosts are genetically intractable. In that cases “heterologous hosts” which are genetically tractable and easily manipulatable with available molecular biological techniques are utilized. Micro-organisms that are typically used within the pharmaceutical industry for heterologous production include: prokaryotes such as Gram negative bacteria (e.g. Escherichia coli) and Gram positive bacteria (e.g. Streptomyces spp, Actinomyces spp), eukaryotes such as filamentous fungi (e.g., Nigrospora spp, Aspergillus spp,) and yeast (e.g. Saccharomyces cereviciae, Pichia pastoris).The “genome mining” approach assisted by rapid advances of genome sequencing has enabled computational mining of genetic data and connect to particular NP, even if they are cryptic or produced in significant titers. Thus, native host, genetically tractable alternative host or suitable heterologous hosts can be used as such microbial platform. Recently “synthetic biology approaches” dealing with designing and construction of new biological systems (e.g. genetic control systems, metabolic pathways, cells) that do not exist in nature and “metabolic engineering approaches” devising optimal metabolic networks or pathways to reengineer the cell factories assist on industrial level production pharmaceuticals from native/heterologous hosts in cost-effective way. Empowered by all these knowledges and techniques the diversity of molecules that can be manufactured is virtually limitless and it opens up new avenues for drug development “from microbial bio-factories”.

Keywords: Microbial cell factories, Metabolic engineering, synthetic biology, heterologous production

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