Abstract
AbstractThe sorbicillinoids are a class of biologically active and structurally diverse fungal polyketides arising from sorbicillin. Through co‐expression of sorA, sorB, sorC, and sorD from Trichoderma reesei QM6a, the biosynthetic pathway to epoxysorbicillinol and dimeric sorbicillinoids, which resemble Diels–Alder‐like and Michael‐addition‐like products, was reconstituted in Aspergillus oryzae NSAR1. Expression and feeding experiments demonstrated the crucial requirement of the flavin‐dependent monooxygenase SorD for the formation of dimeric sorbicillinoids, hybrid sorbicillinoids, and epoxysorbicillinol in vivo. In contrast to prior reports, SorD catalyses neither the oxidation of 2′,3′‐dihydrosorbicillin to sorbicillin nor the oxidation of sorbicillinol to oxosorbicillinol. This is the first report that both the intermolecular Diels–Alder and Michael dimerization reactions, as well as the epoxidation of sorbicillinol are catalysed in vivo by SorD.
Highlights
Sorbicillinoids are an important family of hexaketides produced by terrestrial[1,2] and marine[3,4,5] fungi.[6]
Dimeric sorbicillinoids include bisorbicillinol 3 a, which is formed by an intermolecular Diels–Alder (DA) reaction (Scheme 1 B) and displays radical-scavenging activity almost matching that of a-tocopherol.[16]
ARTEMIS analysis shows that the two sorD genes are not homologous (Scheme 1 E), indicating that they may catalyse different reactions in T. reesei and P. chrysogenum, despite both fungi synthesizing a similar variety of sorbicillinoids.[20,21]
Summary
The only other confirmed homologous sorbicillinoid BGC exists in T. reesei QM6a[21] and shares the three core genes sorA, sorB and sorC required for formation of 2 (Scheme 1 E).[9,20,21,22] The T. reesei BGC encodes a second FMO named SorD. ARTEMIS analysis shows that the two sorD genes are not homologous (Scheme 1 E), indicating that they may catalyse different reactions in T. reesei and P. chrysogenum, despite both fungi synthesizing a similar variety of sorbicillinoids.[20,21] the precise role of SorD has not yet been elucidated. Gulder et al.[24,25] showed conclusively that in vitro production of 2 a by SorC, forms different dimeric sorbicillinoids depending on the organic co-solvent added to the reaction.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
