INSIGHTS | PERSPECTIVES
sciencemag.org SCIENCEPHOTO: RAGNAR TH. SIGURDSSON/AGEFOTOSTOCK/NEWSCOMrapid 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
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Catal. 7 , 710 (2017). - S. Gandomkar, A. Żadło-Dobrowolska, W. Kroutil,
ChemCatChem 11 , 225 (2019). - P. Both et al., Angew. Chem. Int. Ed. 55 , 1511 (2016).
- M. A. Huffman et al., Science 366 , 1255 (2019).
- C. K. Savile et al., Science 329 , 305 (2010).
- F. H. Arnold, Angew. Chem. Int. Ed. 57 , 4143 (2018).
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ACKNOWLEDGMENTS
J.R. acknowledges the School of Chemistry, University
College Dublin, for support.
10.1126/science.aaz7376VOLCANOLOGYCalderas collapse as
magma flows into rifts
Recent caldera collapses show the
importance of distant volcanic rift zones
By Freysteinn SigmundssonM
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. Andersonet 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 ofNordic 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 AAASon December 12, 2019^http://science.sciencemag.org/Downloaded from