Melatonin biosynthesis pathways in nature and its production in engineered microorganisms

Xie, Xiao-Tong; Ding, Dongqin; Bai, Danyang; Zhu, Yaru; Sun, Wei; Sun, Yumei; Zhang, Dawei

doi:10.1016/j.synbio.2021.12.011

Cited by 32 publications

(25 citation statements)

References 124 publications

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“…The important clinical point is that even though tryptophan levels in the diet may be substantially higher than that of melatonin, the conversion from tryptophan to serotonin and ultimately to melatonin may not be efficient in all individuals due to the enzymes involved. The enzyme that catalyzes N -acetyl-serotonin into melatonin is N -acetylserotonin methyltransferase (ASMT) [ 201 ]. Because methyltransferases rely on the biochemical integrity of methylation reactions in the body to transfer a single-carbon unit, the completeness of that conversion will be determined by an individual’s gene variants related to that enzyme.…”

Section: Therapeutic Considerationsmentioning

confidence: 99%

“…The industrial process outlined by various patents typically indicates the use of toxic solvents or petrochemical-derived substrates [ 263 ]. There are also concerns about yielding pollution and these processes’ overall negative environmental impact [ 201 ]. Because various manufacturers are aware of these constraints, different research groups are seriously attempting to streamline the steps involved.…”

Section: Therapeutic Considerationsmentioning

confidence: 99%

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Is Melatonin the “Next Vitamin D”?: A Review of Emerging Science, Clinical Uses, Safety, and Dietary Supplements

Minich

Henning²,

Darley

et al. 2022

Nutrients

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Melatonin has become a popular dietary supplement, most known as a chronobiotic, and for establishing healthy sleep. Research over the last decade into cancer, Alzheimer’s disease, multiple sclerosis, fertility, PCOS, and many other conditions, combined with the COVID-19 pandemic, has led to greater awareness of melatonin because of its ability to act as a potent antioxidant, immune-active agent, and mitochondrial regulator. There are distinct similarities between melatonin and vitamin D in the depth and breadth of their impact on health. Both act as hormones, affect multiple systems through their immune-modulating, anti-inflammatory functions, are found in the skin, and are responsive to sunlight and darkness. In fact, there may be similarities between the widespread concern about vitamin D deficiency as a “sunlight deficiency” and reduced melatonin secretion as a result of “darkness deficiency” from overexposure to artificial blue light. The trend toward greater use of melatonin supplements has resulted in concern about its safety, especially higher doses, long-term use, and application in certain populations (e.g., children). This review aims to evaluate the recent data on melatonin’s mechanisms, its clinical uses beyond sleep, safety concerns, and a thorough summary of therapeutic considerations concerning dietary supplementation, including the different formats available (animal, synthetic, and phytomelatonin), dosing, timing, contraindications, and nutrient combinations.

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Section: Therapeutic Considerationsmentioning

confidence: 99%

Section: Therapeutic Considerationsmentioning

confidence: 99%

Is Melatonin the “Next Vitamin D”?: A Review of Emerging Science, Clinical Uses, Safety, and Dietary Supplements

Minich

Henning²,

Darley

et al. 2022

Nutrients

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show abstract

“…These enzymes regulate the synthesis of pineal melatonin in a circadian fashion. The synthesis of melatonin in the pineal gland involves the sequential conversion of L-tryptophan into hydroxytryptophan by the action of the TPH enzyme, followed by the formation of serotonin by the decarboxylase enzyme [ 15 ]. Tryptophan hydroxylase (TPH1 and TPH2) is the rate-limiting enzyme in the synthesis of serotonin and plays an important role in the nocturnal synthesis of melatonin in the pineal gland.…”

Section: Discussionmentioning

confidence: 99%

“…Melatonin synthesis involves the conversion of the amino acid tryptophan through the intermediate metabolite serotonin and is initiated by the enzyme tryptophan hydroxylase, which is essential for normal sleep/wake cycles. Aralkylamine-N-acetyltransferase (AANAT) and acetylserotonin O-methyltransferase (ASMT) are responsible for the conversion of serotonin to melatonin [ 15 ]. The activity of AANAT increases up to 100-fold in rat pineal glands during the night after turning off the lights, and its activity decreases sharply to the daytime levels within a few minutes after light is re-established [ 16 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

Blast Exposure Dysregulates Nighttime Melatonin Synthesis and Signaling in the Pineal Gland: A Potential Mechanism of Blast-Induced Sleep Disruptions

et al. 2022

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Blast-induced traumatic brain injury (bTBI) frequently results in sleep-wake disturbances. However, limited studies have investigated the molecular signaling mechanisms underlying these sleep disturbances, and potentially efficacious therapies are lacking. We investigated the levels of melatonin and genes involved in melatonin synthesis pathway in the pineal glands of Sprague Dawley rats exposed to single and tightly coupled repeated blasts during the night and daytime. Rats were exposed to single and tightly coupled repeated blasts using an advanced blast simulator. The plasma, cerebrospinal fluid (CSF), and pineal gland were collected at 6 h, 24 h, or 1 month postblast at two different time points: one during the day (1000 h) and one at night (2200 h). Differential expressions of genes involved in pineal melatonin synthesis were quantified using quantitative real-time polymerase chain reaction (qRT-PCR). Plasma and CSF melatonin levels were assessed using a commercial melatonin ELISA kit. The plasma and CSF melatonin levels showed statistically significant decreases at 6 h and 24 h in the blast-exposed rats euthanized in the night (in dim light), with no significant alterations noted in rats euthanized in the morning (daylight) at all three-time points. Blast-exposed rats showed statistically significant decreases in Tph1, Aanat, Asmt, and Mtnr1b mRNA levels, along with increased Tph2 mRNA, in the pineal gland samples collected at night at 6 h and 24 h. No significant changes in the mRNA levels of these genes were noted at 1 month. These findings imply that the melatonin circadian rhythm is disrupted following blast exposure, which may be a factor in the sleep disturbances that blast victims frequently experience.

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“…Melatonin ( N-acetyl-5-methoxytryptamine ) contains two functional groups that result in its specificity and amphiphilicity ie, the 5-methoxy group and the N-acetyl side chain. 25 Although the metabolic machinery to produce melatonin is found in a wide range of tissues circulating melatonin is derived from the pineal gland. The body’s master clock located in the hypothalamic suprachiasmatic nuclei (SCN) regulates melatonin production in the pineal.…”

Section: Introductionmentioning

confidence: 99%

Melatonin’s Benefits and Risks as a Therapy for Sleep Disturbances in the Elderly: Current Insights

Cardinali¹,

Brown²,

Pandi-Perumal³

2022

NSS

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Aging is accompanied by circadian changes, including disruptive alterations in the sleep/wake cycle, as well as the beginning of low-degree inflammation (“inflammaging”), a scenario that leads to several chronic illnesses, including cancer, and metabolic, cardiovascular, and neurological dysfunctions. As a result, any effective approach to healthy aging must consider both the correction of circadian disturbance and the control of low-grade inflammation. One of the most important prerequisites for healthy aging is the preservation of robust circadian rhythmicity (particularly of the sleep/wake cycle). Sleep disturbance disrupts various activities in the central nervous system, including waste molecule elimination. Melatonin is a chemical with extraordinary phylogenetic conservation found in all known aerobic creatures whose alteration plays an important role in sleep changes with aging. Every day, the late afternoon/nocturnal surge in pineal melatonin helps to synchronize both the central circadian pacemaker found in the hypothalamic suprachiasmatic nuclei (SCN) and a plethora of peripheral cellular circadian clocks. Melatonin is an example of an endogenous chronobiotic substance that can influence the timing and amplitude of circadian rhythms. Moreover, melatonin is also an excellent anti-inflammatory agent, buffering free radicals, down-regulating proinflammatory cytokines, and reducing insulin resistance, among other things. We present both scientific and clinical evidence that melatonin is a safe drug for treating sleep disturbances in the elderly.

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Melatonin biosynthesis pathways in nature and its production in engineered microorganisms

Cited by 32 publications

References 124 publications

Is Melatonin the “Next Vitamin D”?: A Review of Emerging Science, Clinical Uses, Safety, and Dietary Supplements

Is Melatonin the “Next Vitamin D”?: A Review of Emerging Science, Clinical Uses, Safety, and Dietary Supplements

Blast Exposure Dysregulates Nighttime Melatonin Synthesis and Signaling in the Pineal Gland: A Potential Mechanism of Blast-Induced Sleep Disruptions

Melatonin’s Benefits and Risks as a Therapy for Sleep Disturbances in the Elderly: Current Insights

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