The natural product biosynthesis potential of the microbiomes of Earth – Bioprospecting for novel anti-microbial agents in the meta-omics era

Abstract

Graphical abstract

Long-Read Metagenome-Assembled Genomes Improve Identification of Novel Complete Biosynthetic Gene Clusters in a Complex Microbial Activated Sludge Ecosystem

“…Conclusion and future perspectives . Uncultured environmental microorganisms have huge potential for SM discovery and yet are understudied, despite the urgency of increasing resistance to current antibiotics and pesticides and the associated risks to humans and agriculture ( 9 , 16 ). AS is an important resource worldwide, mostly for cleaning water and protecting human and environmental health, but it is also increasingly valued for nutrient and water recovery and its contribution to the desired circular economy.…”

“…The uncultured majority of environmental microorganisms has huge untapped potential for the discovery of novel BGCs and, hence, novel bioactive compounds ( 9 , 15 , 16 ). The bioinformatic tools for BGC detection and classification, antiSMASH ( 17 ) and BiG-SCAPE ( 18 ), are used by the majority of metagenome studies and are continuously being improved.…”

Deep-Sea Sediments from the Southern Gulf of Mexico Harbor a Wide Diversity of PKS I Genes

“…Degenerate primers are usually used to identify KS and ACP domains in biodiversity studies or for the identification of new biosynthetic clusters [ 29 ], which limits the information available on the rest of the domains, especially the DH and TE domains. The correspondence analysis conducted by the present study indicates a limited presence of said domains (DH and TE) in the sediments and a lower ratio of the remaining domains of interest (KS, ACP, AT, ER, KR, and MT).…”

Targeted Discovery of Cryptic Metabolites with Antiproliferative Activity

“…Bacteria have been a particularly rich source, revealing thousands of orphan biosynthetic gene clusters (BGCs) that remain to be mined. Most BGCs, however, are silent or sparingly expressed under standard laboratory growth conditions, making it difficult to identify their cognate products. − These realizations have motivated intense efforts to devise methods that can uncover the encoded cryptic metabolites. Over the past decade, a suite of strategies has emerged, which fall into four categories: manipulation of culture conditions, heterologous expression including biosynthetic pathway reconstitution, genetics-dependent methods, and chemical genetics approaches. , Among the latter category, we have contributed high-throughput elicitor screening (HiTES), a flexible approach that identifies small-molecule elicitors of silent BGCs in a forward chemical genetics screen .…”