Microbial production of beneficial indoleamines (serotonin and melatonin) with potential application to biotechnological products for human health

Abstract

Microorganisms have showed the ability to produce biologically active compounds associated with neurotransmission in higher organisms. In particular, serotonin-and melatonin-producing microbes are valuable sources for the development of eco-friendly bioproducts. Serotonin and melatonin are indoleamines that have received special attention due to their positive effects on human health. These biomolecules exert a critical role in several physiological or pathological processes, including some mental and neurological disorders. This article includes a review of the microbial production of serotonin and melatonin, their functions in microorganisms, and their potential uses as therapeutic and/or preventive agents to improve human health. A description of the quantification methods employed to detect indoleamines and the evidence found concerning their microbial production at lab and industrial scale-for application in biotechnological productsis also provided. The microbial ability to synthesize beneficial indoleamines should be further studied and harnessed, in order to allow the development of sustainable bioprocesses to produce foods and pharmaceuticals for human health.

Enzyme Promiscuity in Serotonin Biosynthesis, From Bacteria to Plants and Humans

“…Furthermore, detection and quantification of serotonin and melatonin is still very challenging as these compounds are usually produced in low quantities and the samples are often difficult to analyze. Thus, more effective techniques (or optimization of those in use) that allow the simple and unambiguous quantification of serotonin and melatonin (and their biosynthetic intermediates) in bacteria are essential ( Danilovich et al, 2021 ).…”

“…Dysregulation of serotonergic signaling pathways has been previously implicated in many psychiatric and neurological conditions such as pain, sleep problems, appetite and mood variations ( Athar, 2010 ), and disorders like depression, anxiety, schizophrenia, attention deficit hyperactivity disorder (ADHD), obsessive compulsive disorder (OCD), migraine headache, autism spectrum disorders (ASD; Pourhamzeh et al, 2021 ), bipolar disorder (BP) and addictive behavior ( Lin et al, 2014 ). Serotonin depletion has also been implicated in neurodegenerative diseases, such as Alzheimer’s disease, as serotonin levels decrease with age and neuroinflammation processes have been associated with reduction of serotonin precursors in the CNS ( Danilovich et al, 2021 ). Additionally, lower levels of serotonin have been detected in fibromyalgia patients, where this imbalance has also been associated with other key symptoms such as fatigue and cognitive deficits ( Welsch et al, 2018 ).…”

“…Melatonin levels dysfunction is most associated with sleep disorders. However, as it controls multiple systemic circadian rhythm-dependent processes, its deregulation is also implicated in other conditions such as epilepsy, autism, anxiety, bipolar disorder, and depression ( Danilovich et al, 2021 ).…”

“…Due to its cellular protection and damage repair activity, melatonin has also shown to be effective in preventing tumorigenic mutations in animal models of cancer. Moreover, this indolamine has also been indicated as an effective coadjuvant therapeutic in gut diseases and in parasitic infections, due to its link with the immune system ( Danilovich et al, 2021 ).…”

“…Melatonin’s main role in microbes seems to be related to antioxidant protection, and it also seems to contribute to circadian rhythm regulation in certain human gut bacterial species, as dark conditions seem to lead to increasing levels of this molecule. As these indolamines have demonstrated such beneficial effects in microbial survival, it would be evolutionarily favorable for these organisms to retain the capacity to synthetize such important compounds ( Danilovich et al, 2021 ). Serotonin and melatonin functions in bacteria are summarized in Table 1 .…”