Ellerhorst Mark, Nikitushkin Vadim, Al-Jammal Walid K, Gregor Lucas, Vilotijević Ivan, Lackner Gerald
Chair of Biochemistry of Microorganisms, University of Bayreuth, Germany.
Institute for Organic Chemistry and Macromolecular Chemistry, Friedrich Schiller University Jena, Germany.
Nat Prod Rep. 2025 Aug 13;42(8):1344-1366. doi: 10.1039/d5np00012b.
Covering: 2011 to 2025The importance of redox cofactors like nicotinamide adenine dinucleotide or flavin adenine dinucleotide as cofactors for enzymatic reactions in living organisms is widely known. However, many microbial species also employ unusual redox cofactors such as the coenzyme F or the peptide-derived pyrroloquinoline quinone (PQQ). In this review, we introduce the reader to the recently discovered bacterial redox cofactor mycofactocin (MFT), a valine-tyrosine-derived small molecule of the class of ribosomally synthesized and post-translationally modified peptides (RiPPs) with remarkable biosynthetic and functional similarities to PQQ. The cofactor plays an important role in the reoxidation of non-exchangeable nicotinamide redox cofactors of specialized oxidoreductases in mycobacteria and related actinobacteria. We highlight the bioinformatic discovery of the mycofactocin gene cluster and its auxiliary genes, present strategies for the chemical synthesis of the cofactor, and take a detailed look at the biosynthesis of the glycosylated molecule. Subsequently, the diverse mycofactocin-inducing conditions and associated oxidoreductase families are reviewed, and a potential electron transfer route from high-energy alcohols mycofactocin to oxygen as a final electron acceptor is presented. The review concludes with a comparison of the physiological roles of PQQ and MFT, and an outlook for future research questions and potential biotechnological applications of mycofactocin.
2011年至2025年
烟酰胺腺嘌呤二核苷酸或黄素腺嘌呤二核苷酸等氧化还原辅因子作为生物体内酶促反应的辅因子，其重要性广为人知。然而，许多微生物物种还使用不寻常的氧化还原辅因子，如辅酶F或肽衍生的吡咯喹啉醌（PQQ）。在本综述中，我们向读者介绍最近发现的细菌氧化还原辅因子霉菌因子（MFT），它是一种缬氨酸 - 酪氨酸衍生的小分子，属于核糖体合成和翻译后修饰肽（RiPPs）类别，与PQQ具有显著的生物合成和功能相似性。该辅因子在分枝杆菌和相关放线菌中专门氧化还原酶的不可交换烟酰胺氧化还原辅因子的再氧化中起重要作用。我们重点介绍了霉菌因子基因簇及其辅助基因的生物信息学发现，介绍了该辅因子的化学合成策略，并详细研究了糖基化分子的生物合成。随后，综述了多种诱导霉菌因子的条件和相关的氧化还原酶家族，并提出了从高能醇 霉菌因子到作为最终电子受体的氧气的潜在电子传递途径。综述最后比较了PQQ和MFT的生理作用，并展望了霉菌因子未来的研究问题和潜在的生物技术应用。
