dc.contributor.author | Arsın, Sıla | |
dc.contributor.author | Pollari, Maija | |
dc.contributor.author | Delbaje, Endrews | |
dc.contributor.author | Jokela, Jouni | |
dc.contributor.author | Wahlsten, Matti | |
dc.contributor.author | Permi, Perttu | |
dc.contributor.author | Fewer, David | |
dc.date.accessioned | 2024-09-12T07:01:35Z | |
dc.date.available | 2024-09-12T07:01:35Z | |
dc.date.issued | 2024 | |
dc.identifier.citation | Arsın, S., Pollari, M., Delbaje, E., Jokela, J., Wahlsten, M., Permi, P., & Fewer, D. (2024). A refactored biosynthetic pathway for the production of glycosylated microbial sunscreens. <i>RSC Chemical Biology</i>, <i>Early online</i>. <a href="https://doi.org/10.1039/d4cb00128a" target="_blank">https://doi.org/10.1039/d4cb00128a</a> | |
dc.identifier.other | CONVID_242697534 | |
dc.identifier.uri | https://jyx.jyu.fi/handle/123456789/97057 | |
dc.description.abstract | Mycosporine-like amino acids (MAAs) are a family of water-soluble and colorless secondary metabolites, with high extinction coefficients, that function as microbial sunscreens. MAAs share a cyclohexinimine chromophore that is diversified through amino acid substitutions and attachment of sugar moieties. The genetic and enzymatic bases for the chemical diversity of MAAs remain largely unexplored. Here we report a series of structurally distinct MAAs and evidence for an unusual branched biosynthetic pathway from a cyanobacterium isolated from lake sediment. We used a combination of high-resolution liquid chromatography-mass spectrometry (HR-LCMS) analysis and nuclear magnetic resonance (NMR) spectroscopy to identify diglycosylated-palythine-Ser (C22H36N2O15) as the dominant chemical variant in a series of MAAs from Nostoc sp. UHCC 0302 that contained either Ser or Thr. We obtained a complete 9.9 Mb genome sequence to gain insights into the genetic basis for the biosynthesis of these structurally distinct MAAs. We identified MAA biosynthetic genes encoded at two locations on the circular chromosome. Surprisingly, direct pathway cloning and heterologous expression of the complete mysABCJ1D1G1H biosynthetic gene cluster in Escherichia coli (E. coli) led to the production of 450 Da monoglycosylated-palythine-Thr (C18H30N2O11). We reconstructed combinations of the two distant biosynthetic gene clusters in refactored synthetic pathways and expressed them in the heterologous host. These results demonstrated that the MysD1 and MysD2 enzymes displayed a preference for Thr and Ser, respectively. Furthermore, one of the four glycosyltransferases identified, MysG1, was active in E. coli and catalysed the attachment of a hexose moiety to the palythine-Thr intermediate. Together these results provide the first insights into the enzymatic basis for glycosylation of MAAs and demonstrates how paralogous copies of the MysD enzymes allow the simultaneous biosynthesis of specific chemical variants to increase the structural variation in this family of microbial sunscreens. | en |
dc.format.mimetype | application/pdf | |
dc.language.iso | eng | |
dc.publisher | Royal Society of Chemistry (RSC) | |
dc.relation.ispartofseries | RSC Chemical Biology | |
dc.rights | CC BY 3.0 | |
dc.title | A refactored biosynthetic pathway for the production of glycosylated microbial sunscreens | |
dc.type | research article | |
dc.identifier.urn | URN:NBN:fi:jyu-202409125936 | |
dc.contributor.laitos | Bio- ja ympäristötieteiden laitos | fi |
dc.contributor.laitos | Department of Biological and Environmental Science | en |
dc.type.uri | http://purl.org/eprint/type/JournalArticle | |
dc.type.coar | http://purl.org/coar/resource_type/c_2df8fbb1 | |
dc.description.reviewstatus | peerReviewed | |
dc.relation.issn | 2633-0679 | |
dc.relation.volume | Early online | |
dc.type.version | publishedVersion | |
dc.rights.copyright | © 2024 The Author(s). Published by the Royal Society of Chemistry | |
dc.rights.accesslevel | openAccess | fi |
dc.type.publication | article | |
dc.relation.grantnumber | 323435 | |
dc.subject.yso | genomiikka | |
dc.subject.yso | aminohapot | |
dc.subject.yso | auringonsuoja-aineet | |
dc.subject.yso | NMR-spektroskopia | |
dc.subject.yso | biosynteesi | |
dc.subject.yso | massaspektrografia | |
dc.subject.yso | syanobakteerit | |
dc.format.content | fulltext | |
jyx.subject.uri | http://www.yso.fi/onto/yso/p5146 | |
jyx.subject.uri | http://www.yso.fi/onto/yso/p9530 | |
jyx.subject.uri | http://www.yso.fi/onto/yso/p27198 | |
jyx.subject.uri | http://www.yso.fi/onto/yso/p26254 | |
jyx.subject.uri | http://www.yso.fi/onto/yso/p14405 | |
jyx.subject.uri | http://www.yso.fi/onto/yso/p19212 | |
jyx.subject.uri | http://www.yso.fi/onto/yso/p3324 | |
dc.rights.url | https://creativecommons.org/licenses/by/3.0/ | |
dc.relation.doi | 10.1039/d4cb00128a | |
dc.relation.funder | Research Council of Finland | en |
dc.relation.funder | Suomen Akatemia | fi |
jyx.fundingprogram | Academy Project, AoF | en |
jyx.fundingprogram | Akatemiahanke, SA | fi |
jyx.fundinginformation | This project has been funded by the Novo Nordisk Foundation (18OC0034838) granted to D. F. S. A. is funded by the University of Helsinki, Microbiology and Biotechnology Doctoral Programme. E. D. received a doctoral fellowship from the Brazilian Federal Agency for the Support and Evaluation of Graduate Education (CAPES, Finance code 001) and a PRINT Scholarship from CAPES (88887.572010/2020-00). P. P. was supported by the grants from the Jane ja Aatos Erkon säätiö and the Research Council of Finland (323435). | |
dc.type.okm | A1 | |