Introduction
Synthetic biology is gaining ground as a means to engineer and optimize
microorganisms for desirable biotechnological applications, from the
production of high-value chemicals to bioremediation
(Voigt, 2020). A
major focus of this field has been the genetic manipulation of microbial
cells and the communities they form, through the introduction of
synthetic genetic circuits and metabolic pathways
(McCarty and
Ledesma-Amaro, 2019; San León and Nogales, 2022). Somewhat less
attention has been paid to the abiotic environment on which
microorganisms grow, yet the environment is a key element that controls
the traits and properties of microorganisms, and one that can be
exploited to optimize microbial functions in a straightforward manner
(Eng and Borenstein,
2019).
A main challenge for engineering the abiotic environment is its highly
multidimensional nature, which includes physical (Temperature, volume,
flow rate) and biochemical (pH, concentration of all molecular species)
factors. In general, the effect of these different environmental factors
on the behavior of microbial cultures is complex and non-additive.
Microbiologists have long known that the fitness and phenotypic effects
of a particular environmental factor will differ in various
environmental contexts. To provide just one iconic example, Monod
famously showed that the effect of lactose on the growth rate ofE. coli is initially negligible when glucose is also present,
despite its strong growth-promoting effects when glucose is absent
(Monod, 1942).
Glucose and lactose do not combine additively, as the former masks the
effect of the latter.
In situations like the one above, when the effect of a particular
environmental axis on microbial function is modulated by other
environmental axes, we can say that environmental factors “interact”.
This definition of an “interaction” between two environmental factors
may seem to be unusual. After all, glucose and lactose do not chemically
affect one another. Yet, it is in fact the same definition of
interactions (epistasis) that is used in genetics to describe the
analogous situation where the fitness effect of a mutation is altered by
the presence of another
(Sanchez, 2019).
Of course, these environmental interactions have their basis in concrete
molecular mechanisms. Interactions between two environmental factors may
have a direct origin, for instance when an extracellular molecule
chemically modifies another (Fig. 1a). Alternatively, interactions
between environmental factors may be indirect and mediated by the
changes they induce in the state of the genetic network of a cell, as
was the case for the glucose-lactose interaction described above (Fig.
1b). In the case of microbial consortia, an environmental change may
affect collective community functions through a variety of additional
mechanisms. For instance, the presence of an extracellular molecule may
inhibit or stimulate the growth or the gene expression patterns of one
member species, thus influencing its ability to carry out the role it
plays in the community (Fig. 1c).