The evolution of secondary metabolism – a unifying model

Abstract

Why do microbes make secondary products? That question has been the subject of intense debate for many decades. There are two extreme opinions. Some argue that most secondary metabolites play no role in increasing the fitness of an organism. The opposite view, now widely held, is that every secondary metabolite is made because it possesses (or did possess at some stage in evolution) a biological activity that endows the producer with increased fitness. These opposing views can be reconciled by recognizing that, because of the principles governing molecular interactions, potent biological activity is a rare property for any molecule to possess. Consequently, in order for an organism to evolve the rare potent, biologically active molecule, a great many chemical structures have to be generated, most of which will possess no useful biological activity. Thus, the two sides of the debate about the role and evolution of secondary metabolism can be accommodated within the view that the possession of secondary metabolism can enhance fitness, but that many products of secondary metabolism will not enhance the fitness of the producer. It is proposed that secondary metabolism will have evolved such that traits that optimize the production and retention of chemical diversity at minimum cost will have been selected. Evidence exists for some of these predicted traits. Opportunities now exist to exploit these unique properties of secondary metabolism to enhance secondary product diversity and to devise new strategies for biotransformation and bioremediation.

Dried whole-plant Artemisia annua slows evolution of malaria drug resistance and overcomes resistance to artemisinin

“…Moreover, several other mono-and sesquiterpenes in A. annua have shown activity against malaria parasites (45,46). The ability of plants to produce a virtually unlimited diversity of terpenoids by elongations, cyclizations, and secondary chemical transformations increases the potential for redundant and robust parasite-killing activity (27,47).…”

Discovering variation of secondary metabolite diversity and its relationship with disease resistance inCornus floridaL.

“…The less healthy plants may possess genotypes that mediate metabolism of biosynthetic pathways in ways contributing to less constitutively expressed products—increasing plant susceptibility to initial infections. Higher genetic diversity in certain individuals (e.g., less homozygous genotypes; Figure S7) or subpopulations (e.g., higher rarefied‐allelic richness; Figure 2d) can confer a greater range of gene products (e.g., secondary compound precursors) and increase host ability to respond more readily to any general infection (Firn & Jones, 2000). …”

Catalytic promiscuity in the biosynthesis of cyclic peptide secondary metabolites in planktonic marine cyanobacteria

“…For instance, nonribosomal peptide synthetases and polyketide synthases create secondary metabolites from multienzyme "assembly lines" composed of a series of functional modules acting sequentially, with new domain combinations leading to the generation of unique products (24). In addition, enzymes such as the isoprenoid cyclases can produce multiple products from a single substrate to generate a group of diverse compounds (25,26).…”