68 PEPTIDES
developed a considerable selective advantage,6 and possesses a very high potential for producing sulfur-containing molecules, that Silab decided to beneficially use.
A targeted bioguiding process The company relied on its 20 years of expertise in biotechnologies to develop a unique bioguiding process to specifically stimulate the production of molecules of interest. In this case, the strategy consisted in providing the yeast Ogataea siamensis with cysteine, an amino acid with an atom of sulfur and an indispensable precursor to produce sulfur- containing molecules.
This metabolic engineering approach
required to define several parameters including the dose of inducer, the start, and the duration of the induction. The efficacy of this process was determined by measuring the production of a tracer metabolite – glutathione - by Ogataea siamensis. It was found that the quantity of this tripeptide increased six-fold compared to a process without bioguiding. In addition, to validate the uniqueness
of this approach, the same induction biotechnology process was also applied to other yeast species of the same genus Ogataea or sampled from the phyllosphere of other plants. This comparison validated the choice of Ogataea siamensis as the yeast producing the largest quantities of sulfur- containing molecules. The Ogataea siamensis culture thus
bioguided was then subjected to an enzymatic process. Under the action of a carbohydrase, the cell walls of the yeast were destructured, an essential step for the extraction of the sulfur-containing fraction. Thus, at the scale of the ingredient, the
bioguiding process coupled with enzymatic extraction resulted in an increased level of sulfur-containing peptides, a modification of molecular composition that doubles the original depigmenting efficacy of the active ingredient (Figure 2).
Glycation and pollution, new players in hyperpigmentation While chronological aging and sun exposure have long been described as deregulating melanogenesis and causing hyperpigmentation, new factors have more recently been associated with pigment disorders: pollution and glycation. Particles of pollution are coated with
Polycyclic aromatic hydrocarbons (PAHs) such as benzo(a)pyrene (B[a]P) that can penetrate cell membranes.7
Inside cells, PAHs bind to
the cytosol transcription factor AhR (Aryl- hydrocarbon (Ah) receptor). This binding causes the translocation of
the Ah receptor into the cell nucleus, where it induces the expression of target genes. It has thus been shown that the binding of pollutants to the Ah receptor in melanocytes stimulated melanogenesis8
(Figure 3).
Glycation, for its part, is a reaction during which a bond is created between protein compounds and sugars, thus producing
PERSONAL CARE November 2023
Figure 3: Influence of pollutants and AGEs on pigmentation
Figure 2: Bioguiding process of Ogataea siamensis coupled with enzymatic extraction, resulting in an increased level of sulfur-containing peptides and a doubled depigmenting potential
advanced glycation end-products (AGEs). In the skin, it has been described that the accumulation of AGEs in tissues is caused not only by age but also by photo-exposure.9 The identification of receptors for
AGEs (RAGE) in melanocytes has recently established the connection between glycation and skin pigmentation issues. The interaction between AGEs and these receptors in fact induces melanogenesis10
(Figure 3).
Targeting these two factors is thus a strategy of choice when developing
depigmenting care products, which is the approach that Silab decided to follow with its Ogataea siamensis yeast extract.
Limiting melanogenesis in a context of air pollution The depigmenting efficacy of the Ogataea siamensis yeast extract was determined by studying its capacity to limit tyrosinase activity and melanin synthesis, key processes of melanogenesis. The study involved a colourimetric assay. Tested at 0.5% on Caucasian human
melanocytes treated with a solution of IBMX (3-isobutyl-1-methyl xanthine) to stimulate melanogenic activity, the ingredient significantly limits tyrosinase activity by 88% and melanin synthesis by 90%. Tested at 1% on Asian human melanocytes, it also significantly reduces these two parameters by 21% and 24%, respectively. These results confirm the depigmenting
effect of the active ingredient, an efficacy also shown in contexts of pollution and glycation. In fact, tested at 0.5% on pigmented Silabskin® RE reconstructed epidermis exposed to pollution using a solution of benzo[a]pyrene (B[a]P), the Ogataea siamensis yeast extract significantly limits melanin synthesis by 98% (Figure 4). In addition, tested on melanocytes exposed
to methylglyoxal (precursor of AGEs), the active ingredient limits the activity of tyrosinase by
www.personalcaremagazine.com Figure 1: Metabolism of the yeast Ogataea siamensis in the phyllosphere
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