{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T17:36:42Z","timestamp":1787161002568,"version":"build-2736575974"},"reference-count":66,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T00:00:00Z","timestamp":1768867200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Directorate General for Research, Universidad de La Sabana","award":["ING-89-2025"],"award-info":[{"award-number":["ING-89-2025"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Tyrosinase (EC 1.14.18.1) is a binuclear copper enzyme responsible for the rate-limiting steps of melanogenesis, catalyzing the hydroxylation of L-tyrosine and oxidation of L-DOPA into o-quinones that polymerize melanin. Beyond its physiological role in pigmentation, tyrosinase is also implicated in food browning and oxidative stress\u2013related disorders, making it a key target in cosmetic, food, and biomedical industries. This systematic review, conducted following PRISMA guidelines, aimed to identify and analyze microbial metabolites with tyrosinase inhibitory potential as sustainable alternatives to conventional inhibitors such as hydroquinone and kojic acid. Literature searches in Scopus and Web of Science (March 2025) yielded 156 records; after screening and applying inclusion criteria, 11 studies were retained for analysis. The inhibitors identified include indole derivatives, phenolic acids, peptides, and triterpenoids, mainly produced by fungi (e.g., Ganoderma lucidum, Trichoderma sp.), actinobacteria (Streptomyces, Massilia), and microalgae (Spirulina, Synechococcus). Reported IC50 values ranged from micromolar to milli-molar levels, with methyl lucidenate F (32.23 \u00b5M) and p-coumaric acid (52.71 mM). Mechanisms involved competitive and non-competitive inhibition, as well as gene-level regulation. However, methodological heterogeneity, the predominance of mushroom tyrosinase assays, and limited human enzyme validation constrain translational relevance. Computational modeling, site-directed mutagenesis, and molecular dynamics are proposed to overcome these limitations. Overall, microbial metabolites exhibit promising efficacy, stability, and biocompatibility, positioning them as emerging preclinical candidates for the development of safer and more sustainable tyrosinase inhibitors.<\/jats:p>","DOI":"10.3390\/ijms27021016","type":"journal-article","created":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T11:27:58Z","timestamp":1768908478000},"page":"1016","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Potential Bioactive Function of Microbial Metabolites as Inhibitors of Tyrosinase: A Systematic Review"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-7196-6106","authenticated-orcid":false,"given":"Sofia","family":"Barcenas-Giraldo","sequence":"first","affiliation":[{"name":"Master Program in Process Design and Management, School of Engineering, Universidad de La Sabana, Ch\u00eda 140013, Colombia"},{"name":"Bioprospecting Research Group, School of Engineering, Universidad de La Sabana, Chia 140013, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa","family":"Baez-Leguizamon","sequence":"additional","affiliation":[{"name":"Bioprospecting Research Group, School of Engineering, Universidad de La Sabana, Chia 140013, Colombia"},{"name":"Chemical Engineering Program, School of Engineering, Universidad de La Sabana, Chia 140013, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Barbosa-Gonzalez","sequence":"additional","affiliation":[{"name":"Bioprospecting Research Group, School of Engineering, Universidad de La Sabana, Chia 140013, Colombia"},{"name":"Chemical Engineering Program, School of Engineering, Universidad de La Sabana, Chia 140013, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelica","family":"Leon-Rodriguez","sequence":"additional","affiliation":[{"name":"Bioprospecting Research Group, School of Engineering, Universidad de La Sabana, Chia 140013, Colombia"},{"name":"Chemical Engineering Program, School of Engineering, Universidad de La Sabana, Chia 140013, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2721-1142","authenticated-orcid":false,"given":"Yovani","family":"Marrero-Ponce","sequence":"additional","affiliation":[{"name":"Facultad de Ingenier\u00eda, Universidad Panamericana, Augusto Rodin No. 498, Insurgentes Mixcoac, Benito Ju\u00e1rez, Mexico City 03920, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9588-9935","authenticated-orcid":false,"given":"Luis","family":"Diaz","sequence":"additional","affiliation":[{"name":"Bioprospecting Research Group, School of Engineering, Universidad de La Sabana, Chia 140013, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Zou, C., Li, J., Wang, Y., Zhang, Y., Liu, X., Chen, H., Sun, Y., Zhao, L., Xu, F., and Wang, Q. 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