Microbial Non-Ribosomal Synthesis of Secondary Metabolites

Dear Colleagues,

Microbial secondary metabolites are natural products displaying various therapeutically or agrochemically relevant biological activities (e.g., antibiotics, antifungal or anti-proliferative agents, siderophores, toxins). Interestingly, bacteria and fungi produce many of these compounds courtesy of non-ribosomal biosynthetic enzymatic pathways involving multimodular mega-enzymes called non-ribosomal peptide synthetases and polyketide synthases. These mega-enzymes exhibit a fascinating thiotemplate-based characteristic architecture that permits the iterative assembly of proteinogenic or non-proteinogenic building blocks (e.g., aminoacids, hydroxyacids, acyl-thioesters, fatty acids, chromophores) into growing polypeptidic or polyketid chains as in an assembly line. To date, more than 500 different building blocks have been identified in non-ribosomally synthesized secondary metabolites, hence resulting in a near-infinity of complex structures.

Genes encoding these huge synthetases are generally clustered with other genes encoding regulation, immunity, transport or tailoring (among others) proteins, leading to the concept of biosynthetic genes clusters being responsible for the biosynthesis, structural modifications, regulation and transport of the corresponding secondary metabolites. For decades, new secondary metabolites have been discovered through screenings of biological activities, but increasing re-discoveries of already-known secondary metabolites have proven that this strategy has become inefficient lately. However, the current exponential increase of available genomic sequences (including sequences from thousands complete microbial genomes) suddenly gives access to a huge amount of information which unravels the potential of microorganisms to produce secondary metabolites exhibiting new structural scaffolds, and therefore new biological activities, which is largely underestimated. Indeed, in silico analyses of these genomes (also known as genome mining) show that most of the biosynthetic genes clusters remain silent under usual laboratory conditions. The actual challenge remains to exploit this potential, as many “awakening” techniques for these silent biosynthetic gene clusters are yet available.

With this Special Issue, we aim at presenting current and future directions in understanding the non-ribosomal biosynthesis of microbial secondary metabolites. This includes but is not limited to the identification of new biosynthetic pathways in microbial genomes, the deciphering of these pathways, the structural elucidation of the synthesized compounds, the functional characterization of the biosynthetic mega-enzymes and their products, or the use of synthetic biology to generate structural analogues of the natural products.

As the Guest Editors of this Special Issue, we kindly invite you to submit research articles, review articles, and short communications related to the field of non-ribosomal synthesis of secondary metabolites.

Dr. Stéphane Cociancich
Prof. Valérie Leclère
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Microorganisms is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.