Capturing Natural Product Biosynthetic Pathways from Uncultivated Symbiotic Bacteria of Marine Sponges Through Metagenome Mining: A Mini-Review
Abstract: Symbiotic bacteria
associated with marine sponges have frequently been proposed as the true
producer of many bioactive natural products with potent anticancer activities.
However, the majority of these complex symbiotic bacteria cannot be cultivated
under laboratory conditions, hampering efforts to access and develop their
potent compounds for therapeutic applications. Metagenome mining is a powerful
cultivation-independent tool that can be used to search for new natural product
biosynthetic pathways from highly complex bacterial consortia. Some notable
examples of natural products, in which their biosynthetic pathways have been
cloned by metagenome mining are onnamide A, psymberin, polytheonamides,
calyculin, and misakinolide A. Subsequent expression of the pathways in easily
culturable bacteria, such as Escherichia coli, could lead to the sustainable
production of rare promising natural products. This review discusses principles
of metagenome mining developed to gain access to natural product biosynthetic
pathways from uncultured symbiotic bacteria of marine sponges. This includes
detecting biosynthetic genes in sponge metagenome, creating large metagenomic
library, rapid screening of metagenomic library, and clone sequencing. For many
natural products made by modular polyketide synthases (PKSs) and hybrids with
non-ribosomal peptide synthetases (NRPSs), their biosynthetic pathways as well
as structures of final products can be predicted with high accuracy through
bioinformatic analysis and sometimes combined with functional proof. Further
metagenome sequencing integrated with single-cell analysis and chemical studies
could provide insights into the remarkable biosynthetic capacity of
uncultivated bacterial symbionts, thereby facilitating the discovery and
sustainable production of a wide diversity of sponge-derived complex compounds.
Keywords: Marine sponges,
natural product biosynthetic pathway, uncultured symbiotic bacteria, metagenome
mining
Author: Agustinus Robert Uria
Journal Code: jpperikanangg150036
