(654.14) Structural Investigation of AlsA, a Radical S-adenosylmethionine Enzyme Involved in the Biosynthesis of the Oxetane-containing Herbicide Albucidin

Poster Board Number: A165

Dante Avalos (Howard Hughes Medical Institute, Howard Hughes Medical Institute), Po-Hsun Fan (University of Texas at Austin), Yujie Geng (University of Texas at Austin), Hung-wen Liu (University of Texas at Austin), Catherine Drennan (Howard Hughes Medical Institute, Howard Hughes Medical Institute, Howard Hughes Medical Institute)

Herbicides are a class of molecules commonly employed to maintain high crop yields by targeting weeds, a particularly damaging class of pests in agriculture. Albucidin is a novel herbicide found in Streptomyces albus subsp. Chlorinus NRRL B-24108 that shows a suspected new mode of action. Albucidin is a nucleoside analogue containing an oxetane moiety similar to the antiviral compound oxetanocin-A (OXT-A). OXT-A is the only other known naturally occurring oxetane-containing nucleoside analogue and has a biosynthetic pathway with two key enzymes: OxsA and OxsB. OsxB is a B12-dependent radical S-adenosylmethionine (RS) enzyme and catalyzes formation of the oxetane ring via an oxidative ring contraction. A similar reaction has been proposed to be catalyzed by the B12-dependent RS enzyme AlsB in the biosynthetic pathway of albucidin; however, the two biosynthetic pathways appear to diverge at this point as well. While OXT-A is formed upon subsequent reduction and OxsA catalyzed dephosphorylation of the OxsB reaction product, the chemistry leading to albucidin is much less clear. In particular, one carbon must be eliminated, and AlsA, which is a biotin synthase-like RS enzyme also encoded in the albucidin biosynthetic cluster, has been proposed to participate in this reaction. AlsA is most closely related to BioB-like enzymes and demonstrates high sequence similarity with the canonical TIM barrel domain; however, AlsA also contains an N-terminal domain of about 100 amino acids that shares minimal sequence homology to other RS enzymes with known structures. Herein, recent developments in the structural analysis of AlsA using X-ray crystallography are reported.

Support or Funding Information

This work was supported in part by a grant to the Massachusetts Institute of Technology from the Howard Hughes Medical Institute through the James H. Gilliam Fellowships for Advanced Study program.

lt;div class="page" title="Page 25"gt; lt;div class="layoutArea"gt; lt;div class="column"gt; lt;pgt;lt;span style="font-size: 14pt; font-family: Calibri;"gt;This work was supported in part by a grant to the Massachusetts Institute of Technology from the Howard Hughes Medical Institute through the James H. Gilliam Fellowships for Advanced Study programlt;/spangt;lt;span style="font-size: 14pt; font-family: Calibri;"gt;. lt;/spangt;lt;/pgt; lt;/divgt; lt;/divgt; lt;/divgt;