Science - USA (2021-11-05)

(fig. S23) are universal sentinels of the nucleic acid–mediated innate immune response and activate key inflammatory pathways. F ...

endymocytes and peptidocytes, originated via cell type diversification. These evolu- tionary lineages are distinct from develop- ...

S. Nakayamaet al.,Curr. Biol. 25 , 2549–2554 (2015). T. Kawahara, M. T. Quinn, J. D. Lambeth,BMC Evol. Biol. 7 , 109 – 121 (200 ...

enzymes to act on the growing chain. Therefore, the movement of ACP and the specific inter- actionsthatACPformswithotherdomainsi ...

the equivalent domains in Lsd14 with and without the prime symbol (′) for clarity. How- ever, only DD-KS-LD-AT-PAL (chain A) and ...

(KR) 2. Overall, the asymmetric domain orga- nization in Lsd14 indicates that its two reaction chambers operate asynchronously, ...

toward KS′in reaction chamber I, whereas the active site entrance of KR faces away from either reaction chamber (fig. S11). (DE- ...

with each Fab making contact with DD, KS, and AT, similar to the crystal structure of DEBS module 3 (DD-KS-LD-AT) 2 bound to 1B2 ...

from a DEBS PKS and then applying the Fab fragment that binds to the DEBS docking do- main. By comparison, our crystal structure ...

proteins, the trajectory of a growing poly- ketide chain as it is channeled from one co- valently bound state to the next ( 5 ). ...

uncharacterized domain-domain interfaces. Perhaps most unexpectedly, they also re- veal module asymmetry not observed in previou ...

visible KR is attached (Fig. 2B; figs. S12, S13, and S14A; and supplementary text). This KR domain is buttressed by a patch of n ...

consistent with placing a 2(S)-methylmalonyl extender unit favorably for catalysis. We there- fore propose thatState 1is descrip ...

S. Wuet al.,Structure 20 , 582–592 (2012). D. P. Coganet al.,J. Am. Chem. Soc. 142 , 14933– 14939 (2020). A. T. Keatinge-Clay, ...

andC—to outcompete the desired pathway. Second, even if the C–H amination does take place ( 24 ), the resulting enamine moiety w ...

We hypothesized that it would be benefi- cial to have moderate steric hindrance on the NBE—sufficient to inhibit the cyclopropan ...

SCIENCEscience.org 5 NOVEMBER 2021¥VOL 374 ISSUE 6568 737 Fig. 3. Substrate scope.Reaction conditions for alkenyl triflate: alke ...

cyclohexanones ( 18 to 21 ) in good yields, complementary to enone conjugate addi- tion chemistry. Conversely,b-substituted cycl ...

Stimulated by this challenge, we conceived an alternative enone-based strategy (Fig. 4B). Conjugate addition of alkyl nucleophil ...

was found to be optimal (for detailed op- timization, see table S5). Theb-to-amigrated products ( 40 and 41 )wereformedwith comp ...