Recent Advances in the Heterologous Expression of Biosynthetic Gene Clusters for Marine Natural Products

Abstract

Marine natural products (MNPs) are an important source of biologically active metabolites, particularly for therapeutic agent development after terrestrial plants and nonmarine microorganisms. Sequencing technologies have revealed that the number of biosynthetic gene clusters (BGCs) in marine microorganisms and the marine environment is much higher than expected. Unfortunately, the majority of them are silent or only weakly expressed under traditional laboratory culture conditions. Furthermore, the large proportion of marine microorganisms are either uncultivable or cannot be genetically manipulated. Efficient heterologous expression systems can activate cryptic BGCs and increase target compound yield, allowing researchers to explore more unknown MNPs. When developing heterologous expression of MNPs, it is critical to consider heterologous host selection as well as genetic manipulations for BGCs. In this review, we summarize current progress on the heterologous expression of MNPs as a reference for future research.

Mechanisms and applications of microbial synthesis of metal nanoparticles in agri-sectors

“…This can be achieved through rapid screening and identification of microbes with efficient MNP synthesis capabilities using high-throughput screening technologies and genomic sequencing. 284 Additionally, metagenomics approaches are very practical, allowing for the discovery of potential MNP synthesis genes in uncultured microbes by directly extracting DNA from environmental samples for metagenomic sequencing. 285 Second, strengthening the research on the mechanisms of MNPs synthesis by different microbes.…”

Marine fungi: A treasure trove of novel natural products and for biological discovery

“…Over the years, many different methods have been established to induce transcriptional silent gene clusters, including the addition of a physical scaffold, addition of small molecule elicitors, and cocultivation with another microbe [ 20 ]. Yet, another often fruitful approach is heterologous expression of SM gene clusters in a suitable heterologous host, which may require certain genetic manipulations of the SM gene clusters [ 21 ]. Histone methylation also may be responsible for secondary metabolite gene cluster repression [ 22 ].…”

Pentostatin Biosynthesis Pathway Elucidation and Its Application

“…With the rapid development of genome sequencing technology, it has played a very important role in promoting the discovery rate of novel biosynthesis gene clusters of natural products [31,32]. The whole genome sequencing of Streptomyces antibioticus NRRL3238 was completed in 2017 [13].…”