Science - 6 December 2019

INSIGHTS | PERSPECTIVES

sciencemag.org SCIENCE

PHOTO: RAGNAR TH. SIGURDSSON/AGEFOTOSTOCK/NEWSCOM

rapid gene sequencing, and the availabil-
ity of low-cost DNA synthesis have made it
possible to alter the properties of enzymes
and fine-tune them for biocatalytic appli-
cations ( 6 – 8 ). The work by Huffman et al.
is a milestone in cascade design, largely
because of the number of biocatalysts op-
erating in tandem and the engineering
feat required to optimize five of the nine
enzymes involved in the synthesis. It also
highlights how biosynthetic or degradative
pathways can be a source of inspiration for
the design of efficient biocatalytic cascades
and how sequences can be reconstituted
using enzymes recruited from multiple
sources—in this case, of bacterial, fungal,
plant, and mammalian origin. The diverse
role that biocatalysts can play is also exem-
plified in this work, where five engineered
enzymes are directly involved in the syn-
thesis of the target molecule, and four ad-
ditional enzymes function to recycle coen-
zyme, remove inhibitory by-products, and
maintain the correct oxidation state of the
copper cofactor.
Previous approaches reported for the
synthesis of islatravir relied on multistep
syntheses and require protecting group
manipulations and intermediate purifica-
tion steps ( 9 , 10 ). The incorporation of a
key biocatalytic step or steps has the po-
tential to revolutionize synthetic design
strategies by making possible transforma-
tions that are not accessible using solely
chemical approaches ( 11 , 12 ). The applica-
tion of enzymes in industry and the de-
velopment of chemoenzymatic routes to
complex molecules is now well established.
However, multistep syntheses exclusively
comprising biocatalytic transformations
are rare ( 13 ), and this contribution sets a
new standard for the synthesis of complex
molecules with enzymatic cascades. j

REFERENCES AND NOTES

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   Catal. 7 , 710 (2017).


2. S. Gandomkar, A. Żadło-Dobrowolska, W. Kroutil,
   ChemCatChem 11 , 225 (2019).


3. P. Both et al., Angew. Chem. Int. Ed. 55 , 1511 (2016).


4. M. A. Huffman et al., Science 366 , 1255 (2019).


5. C. K. Savile et al., Science 329 , 305 (2010).


6. F. H. Arnold, Angew. Chem. Int. Ed. 57 , 4143 (2018).


7. C. Zeymer, D. Hilvert, Annu. Rev. Biochem. 87 , 131 (2018).


8. C. A. Denard, H. Ren, H. Zhao, Curr. Opin. Chem. Biol. 25 ,
   55 (2015).


9. M. McLaughlin et al., Org. Lett. 19 , 926 (2017).


10. M. Kageyama, T. Nagasawa, M. Yoshida, H. Ohrui, S.
    Kuwahara, Org. Lett. 13 , 5264 (2011).


11. N. J. Turner, E. O’Reilly, Nat. Chem. Biol. 9 , 285 (2013).


12. M. Hönig, P. Sondermann, N. J. Turner, E. M. Carreira,
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13. S. Wu et al., Nat. Commun. 7 , 11917 (2016).

ACKNOWLEDGMENTS
J.R. acknowledges the School of Chemistry, University
College Dublin, for support.

10.1126/science.aaz7376

VOLCANOLOGY

Calderas collapse as

magma flows into rifts

Recent caldera collapses show the

importance of distant volcanic rift zones

By Freysteinn Sigmundsson

M

ajor magma drainage from volca-

noes causes the collapse of volcanic

edifices, forming calderas that can

be both many kilometers wide and

hundreds of meters deep. Many

calderas form during major explo-

sive eruptions, when magma erupts from

fractures on ring faults that bound calderas.

However, the most recent caldera-forming

events at Kı ̄lauea Volcano, Hawai‘i, in 2018

( 1 ) and at Bárðarbunga, Iceland, in 2014–

2015 ( 2 ) formed by a different mechanism.

Both events were gradual caldera collapses

that occurred as magma flowed over long

distances into rifts far away from volcano

summits. The caldera ring faults associated

with collapse only began to move after a

major magma withdrawal into a rift zone.

The detailed monitoring of the recent

Kı ̄lauea collapse reveals the behavior of the

magma plumbing system involved and the

dynamic processes related to coupling a cal-

dera collapse with a rift eruption. Anderson

et al. used modeling of geodetic changes to

give an account of the pressure drop in a

magma body before and during a collapse ( 3 ).

Geochemical analysis of the eruptive prod-

ucts by Gansecki et al. reveal how pockets of

magma of different types were captured by

an advancing dike and erupted at the begin-

ning of activity ( 4 ). Patrick et al. demonstrate

how some of the short-term fluctuations in

eruption activity, witnessed as magma surges,

were a response to pressure variations under

the collapsing caldera ( 5 ). When compared to

observations from Bárðarbunga ( 2 , 6 – 10 ) and

other collapses, a pattern emerges that may

be a typical and common way for calderas to

form at basaltic volcanoes.

The beginning of the process is a large-

scale lateral subsurface injection of magma

into a volcano rift zone, which is a preferred

path of dikes that forms in response to im-

posed stresses. Rift zones are common on

volcanoes and result from the tectonic set-

ting, topography, slope instability, and/or, for

ocean island volcanoes, seaward sliding of a

volcano flank. In Iceland, the divergence of

tectonic plates causes the formation of rift

zones. At Kı ̄lauea Volcano, the cause is the

gradual seaward sliding of the south flank of

Nordic Volcanological Center, Institute of Earth Sciences,

University of Iceland, Reykjavík, Iceland. Email: [email protected]

Lava erupts from a

rift zone fissure during the

2014 – 2015 Bárðarbunga

caldera collapse in Iceland.

1200 6 DECEMBER 2019 • VOL 366 ISSUE 6470

Published by AAAS

on December 12, 2019^

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