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made it straightforward and robust enough

for the authors to prepare structural analogs

of 2 , and in turn 1 , to probe their activity.

Assaying these compounds for antibacte-

rial activity revealed interesting trends. For

example, the sense of chirality of 1 had little

effect, with its enantiomer ent- 1 and meso-

diastereomer displaying a potency similar

to that of natural 1. The dependence on

overall topology rather than absolute chiral-

ity points to a physical interaction underly-

ing their activity.

Although it had been suggested that 1

may target bacterial membranes, no de-

finitive evidence has been available ( 9 ).

D’Angelo et al. prepared a himastatin probe

in which one isopropyl group is replaced

with a fluorescent dye. Antibacterial activity

was only maintained when one half of the

molecule bore this bulky tag. Prior two-di-

rectional approaches would have great dif-

ficulty accessing this heterodimer. Confocal

microscopy experiments in Bacillus subtilis

revealed that himastatin induces mem-

brane defects that ultimately permeabilize

the cell. This mode of action is reminiscent

of that of daptomycin, a structurally unre-

lated cyclic peptide antibiotic ( 10 ).

The concise synthetic route of D’Angelo

et al. should enable in-depth investiga-

tions of structural change to himastatin

that could tune the potency and selectivity.

Additionally, experiments that explore the

molecular basis of the interaction with the

bacterial membrane, as has recently begun

to become apparent for daptomycin ( 11 ),

could provide opportunities for both funda-

mental biophysical discoveries and inform

designs of other molecules for membrane

perturbation. From a synthetic standpoint,

the bold dimerization showcased may in-

spire similarly direct approaches to com-

plex dimeric or oligomeric natural products

by coupling native monomers. j

REFERENCES AND NOTES

1. H. W. Boucher et al., Clin. Infect. Dis. 48 , 1 (2009).


2. G. D. Wright, Can. J. Microbiol. 60 , 147 (2014).


3. P. M. Wright, I. B. Seiple, A. G. Myers, Angew. Chem. Int.
   Ed. 53 , 8840 (2014).


4. K. S. Lam et al., J. Antibiot. (Tokyo) 43 , 956 (1990).


5. K. A. D’Angelo, C. K. Schissel, B. L. Pentelute, M.
   Movassaghi, Science 375 , 894 (2022).


6. T. M. Kamenecka, S. J. Danishefsky, Chemistry 7 , 41
   (2001).


7. S.-M. Yu, W.-X. Hong, Y. Wu, C.-L. Zhong, Z.-J. Yao, Org.
   Lett. 12 , 1124 (2010).


8. A. J. Oelke et al., Chemistry 17 , 4183 (2011).


9. S. W. Mamber et al., Antimicrob. Agents Chemother. 38 ,
   2633 (1994).


10. A. Pokorny, P. F. Almeida, J. Membr. Biol. 254 , 97 (2021).


11. R. Moreira, S. D. Taylor, Angew. Chem. Int. Ed. 61 ,
    e202114858 (2022).

ACKNOWLEDGMENTS

The Welch Foundation (I-2045) and University of Texas

Southwestern Medical Center (W. W. Caruth Jr. Scholarship)

are acknowledged for funding.

10.1126/science.abn8327

By Ferdinando Patat^1 and Michela Mapelli^2

T

o different extents, all celestial bodies

rotate, planets and stars alike. Things

get particularly interesting when the

objects are part of gravitationally

bound configurations such as a bi-

nary system, in which the two bodies

revolve around each other. In the absence of

external perturbations, their rotation axes

tend to be aligned with each other and per-

pendicular to the orbital plane. This trend

is usually true even for exotic systems, such

as x-ray binaries, in which a star revolves

around a black hole. On page 874 of this

issue, Poutanen et al. ( 1 ) present the case

of x-ray binary system MAXI J1820+070,

which counterintuitively has the spin axis

of the black hole strongly misaligned to the

orbital plane. This deeply challenges the

current understanding of how black holes

can be formed and indicates the presence of

a powerful kick produced by the supernova

that generated the black hole.

Our star, the Sun, has no companions. Al-

though one may view this arrangement as

the norm, a large fraction of stellar objects

in a galaxy actually belong to binary or even

triple systems. Multistar systems are more

likely for heavier stars, with about 80% of

stars with masses 15 times larger than that

of the Sun (Msun) being in a multiple sys-

tem ( 2 ). Stars with masses >20Msun are ex-

tremely short-lived, with a typical life span

shorter than 10 million years. During their

brief existence, massive stars in tight binary

systems interact with the companion in sev-

eral ways. For example, one of the two stars

may transfer part of its matter to the other,

changing the mass ratio and other orbital

properties of the system. Tides can arise

when the gravity force exerted by one star

onto the other varies substantially from one

point of the stars’ surface to another, result-

ing in a tidal pull. Tides tend to align their

rotation axes perpendicularly to the orbital

plane of the system.

The death of a massive star, often accom-

panied by a formidable supernova explosion,

is expected to leave behind a very compact

and massive stellar object, such as a black

hole. Because of the powerful asymmetric

mass ejection, the newborn black hole re-

ceives what is known as a “natal kick.” This

kick might tilt the black hole’s rotation axis,

misaligning it with respect to the axis of the

ASTRONOMY

A crooked spinning black hole

New observations challenge the current understanding

of black hole formation

Orbital

plane axis

Accretion disk

Companion

star

Black hole

spin axis

Black hole

A tilted black hole spinning in a binary system

Astronomers have observed a black hole that spins along an axis strongly misaligned

with the orbital plane of the binary system MAXI J1820+070. This challenges current models

on the formation of black holes generated by supernovae.

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