Advances in Biosynthesis of Natural Products from Marine Microorganisms

Abstract

Natural products play an important role in drug development, among which marine natural products are an underexplored resource. This review summarizes recent developments in marine natural product research, with an emphasis on compound discovery and production methods. Traditionally, novel compounds with useful biological activities have been identified through the chromatographic separation of crude extracts. New genome sequencing and bioinformatics technologies have enabled the identification of natural product biosynthetic gene clusters in marine microbes that are difficult to culture. Subsequently, heterologous expression and combinatorial biosynthesis have been used to produce natural products and their analogs. This review examines recent examples of such new strategies and technologies for the development of marine natural products.

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

“…Moreover, many marine strains have low or no expression of BGCs on usual standard media, resulting in low natural yields or the inability to synthesize MNPs [ 131 , 132 , 133 ]. An effective way to mine potential MNPs is through the heterologous expression of BGCs, expressing exogenous target BGCs in characterized hosts, and using advanced genetic engineering techniques to regulate this process [ 13 , 134 , 135 ]. With advances in DNA sequencing technology and bioinformatics tools, researchers have identified a huge potential for untapped MNPs biosynthesis.…”

“…Although the heterologous expression of BGCs in model hosts is a robust way to increase the production of MNPs, it still faces many problems due to the difference between the host and native strains in metabolic regulation, precursor supply, auxiliary factors, and the self-resistance, such as the lack of regulation of gene expression, the difficulty of recruiting the premise modules, and the inefficient transcription and translation of BGCs [ 13 , 33 ]. Therefore, it is important to rationally design and regulate BGCs and heterologous hosts to improve the biosynthetic efficiency of MNPs.…”

“…This technical breakthrough provides new avenues for the mining, modification, and production of MNPs. On the basis of genomics, we can subsequently use molecular techniques to biosynthesize high titers of MNPs, rather than merely using traditional separation and purification techniques to obtain small amounts of chemical compounds [ 13 ]. Genome mining is used to speculate the potential functions of the metabolites guided by BGCs [ 14 , 15 ].…”

Identification of the new prenyltransferase Ubi-297 from marine bacteria and elucidation of its substrate specificity

“…Following up on our recent exploration of the biosynthetic repertoire of marine bacteria [ 14 – 15 ], the diversity of the encoded and yet often unexplored bacterial Ptases of Flavobacteria and Saccharomonospora strains sparked our interest. In this study we investigated three yet poorly described homologous Ptases within the UbiA superfamily and evaluated their substrate scope by heterologous production and enzymatic bioassays.…”

Bromoditerpenes from the Red Seaweed Sphaerococcus coronopifolius as Potential Cytotoxic Agents and Proteasome Inhibitors and Related Mechanisms of Action

“…The efforts in discovering new therapeutic entities from marine origin have driven a growing number of marine natural products and derivatives that entered clinical trials, reinforcing their relevance and impact on the pharmaceutical industry [ 3 ]. The high success ratio of the approved drugs / MNPs reported (1 in 3500 MNPs) compared with the hit rate (1/5000 to 1/10,000) of non-marine-derived NPs indicates their pharmacological relevance [ 4 , 5 ].…”