Screening for tyrosinase inhibitors from actinomycetes; identification of trichostatin derivatives from Streptomyces sp. CA-129531 and scale up production in bioreactor.

Screening for tyrosinase inhibitors from actinomycetes; identification of trichostatin derivatives from Streptomyces sp. CA-129531 and scale up production in bioreactor.
Bioorg Med Chem Lett. 2020 Jan 21;:126952
Authors: Georgousaki K, Tsafantakis N, Gumeni S, Gonzalez I, Mackenzie TA, Reyes F, Lambert C, Trougakos IP, Genilloud O, Fokialakis N
Abstract
In the course of a primary screening of 614 microbial actinomycete extracts for the discovery of tyrosinase inhibitors, the EtOAc extract of the fermentation broth of the strain Streptomyces sp. CA-129531 isolated from a Martinique sample, exhibited in cell free and cell-based assays the most promising activity (IC50 value of 63 μg/mL). Scaled-up production in a bioreactor led to the isolation of one new trichostatic acid analogue, namely trichostatic acid B (1), along with six known trichostatin derivatives (2-7), four diketopiperazines (8-11), two butyrolactones (12-13) and one hydroxamic acid siderophore (14). Among them, trichostatin A (4) showed a Ki value of 6.1 μM and six times stronger anti-tyrosinase activity (IC50 2.18 μΜ) than kojic acid (IC50 14.07 μΜ) used as a positive control. Deoxytrichostatin A (6) displayed also strong inhibitory activity against tyrosinase (IC50 19.18 μΜ). Trichostatin A production in bioreactor started together with the exponential phase of growth (day 4) and the maximum concentration was reached at day 9 (2.67 ± 0.13 μg/mL). Desp...

Source: Bioorganic and Medicinal Chemistry Letters - January 20, 2020 Category: Chemistry Authors: Georgousaki K, Tsafantakis N, Gumeni S, Gonzalez I, Mackenzie TA, Reyes F, Lambert C, Trougakos IP, Genilloud O, Fokialakis N Tags: Bioorg Med Chem Lett Source Type: research