Microbial Involvement in the Production of Natural Products by Plants, Marine Invertebrates and Other Organisms

In the early 1980s, there were occasional reports of natural products isolated from marine invertebrates that were either identical to compounds from terrestrial sources, or were close chemical relatives. Since that time period it has become evident that microbes, whether they can currently be fermented under “normal conditions” or require genetic analyses and subsequent elaboration in surrogate hosts etc., are very heavily involved in the production of marine invertebrate secondary metabolites. In the last few years, the situation with plant-derived natural products is very reminiscent of the early 1980s / marine invertebrate stories, as there are now significant numbers of reports invoking microbes (usually endophytic fungi), in the production of nominally plant-derived natural products. In one particular case, that of maytansine, the production by epiphytic root bacteria in the nominal producing plant is definitive. Each issue of current journals covering genetic analyses of plants or marine invertebrates, often contains at least one article (basic science or review), that furthers the potential involvement of microbes in the production of even well-known molecules such as taxol, vinca alkaloids, homoharringtonine on the plant side and pederin-related (e.g. onnamide) derivatives on the marine side. We will also give information on bacterial, fungal and algal interactions that together lead to the production of natural products, though the exact involvement may not yet be known. We will broadly discuss the current situation and then hone in on areas where microbial involvement is definitive, and give the evidence for areas where it is still circumstantial.

Keywords: Biosynthesis, Biosynthetic gene clusters, Bioactive agents, Coculture, Endophyte, Microbial interactions, Natural products, Sequencing, Symbiont, Unculturable.