INSIGHTS | PERSPECTIVES
By Nigel S. Scrutton
The acceleration of chemical reactions by visible light offers environmentally friendly routes to chemical synthesis that may be practical and scalable for use in industrial manufacture (1). Although widespread in chemistry,
photocatalysis is rare in biology, and the
harnessing of photochemistry in biologically based manufacture is challenging.
On page 903 of this issue, Sorigué et al. (2)
describe an algal photoenzyme that uses
blue light to convert fatty acids into hydrocarbons. The photoenzyme uses a riboflavin (vitamin B2) cofactor to drive fatty acid
decarboxylation via radical-based catalysis
and shows promise as a light-dependent
biocatalyst for hydrocarbon production.
This and other recent discoveries suggest
a hitherto hidden scope for biotechnologically useful photochemistry by means of
Enzyme catalysis is typically thermally
activated and is aided by natural enzyme
cofactors, which are derived from vita-
mins or by posttranslational modifica-
tion of active-site amino acids. These
cofactors, such as the flavins (3), bring a
wealth of reaction capabilities that can-
not be achieved with the 20 amino acids
used for protein biosynthesis. There is a
long history of uncovering diverse reac-
tion mechanisms with biological cofac-
tors, but surprises still emerge. One such
example is the recent discovery of prenyl-
ated flavins that catalyze reversible decar-
boxylation (see the figure) (4), a reaction
outcome—loss of CO2—that is similar to
that reported by Sorigué et al. It remains
to be shown whether established cofactors
such as those derived from riboflavin can
also show unexpected chemical versatility.
In contrast to the expanding chemical
repertoire of thermally activated enzymes,
enzymatic photocatalysis is rare. Only
two photoenzymes have been reported.
The first is photolyase, a DNA repair enzyme that depends on flavin (5). The second, protochlorophyllide oxidoreductase,
is specific to chlorophyll biosynthesis
and uses the substrate protochlorophyllide to capture light (6). Neither enzyme
has obvious relevance to or application in
The lack of natural biological photo-catalysts that can harness clean energy for
biomanufacturing has driven chemists and
biochemists to engineer hybrid systems
that unite the catalytic power of enzymes
with external photochemical, light-responsive chromophores (7). However, these
hybrid systems are often compromised by
poor control of the excited-state chemistry
of the chromophore and poor coupling to
bond breakage and formation in the enzyme’s active site. Applications have generally been restricted to photoreduction of
natural redox cofactors through long-range
electron transfer to drive redox-based bio-transformations (8). A notable exception
is the transformation of a thermally activated, nicotinamide coenzyme–dependent
ketoreductase from a carbonyl reductase
to a photobiocatalyst that can dehaloge-nate lactones enantioselectively in a radical-based reaction (9). This rare example
of new enzyme chemistry accessed through
photobiocatalysis illustrates the potential
of repurposing thermally activated biocatalysts by using light.
Sorigué et al. now show that similar re-
programming can occur naturally. They re-
port that the microalga Chlorella variabilis
contains a newly identified photoenzyme,
DNA exit and RNA exit tunnels (see the fig-
ure). The NGN domain forms a lid on the
DNA-binding channel of RNAPII, thereby
preventing the dissociation of elongation
complexes (10, 11). In addition, Spt4/5
could act as a molecular caliper akin to disc
brakes during promoter proximal pausing.
The third factor included in Ehara et al.’s
study, Elf1, is associated with elongating
RNAPII throughout the genome (12). Elf1
binds close to the NGN domain and thereby
seals the RNAPII DNA entry tunnel entirely
(see the figure). Ehara et al. show that Elf1
exerts an inhibitory effect on elongation,
which hints at a possible role of Elf1 in regulating transcription.
The complete elongation complex structure explains why mutations in Elf1, TFIIS,
and Spt4/5 enhance each other, a phenomenon called synthetic lethality, which often
implies that components interact physically, functionally, or both (13).
The eukaryotic and archaeal transcription machineries are closely related (2). Archaea use a smaller subset of factors than
eukaryotes, but these typically correspond
to a minimal configuration of factors that
enable the most fundamental RNA polymerase functions during the transcription
cycle. The conserved factors include all
three elongation factors described in Ehara
et al.’s study. Therefore, the structure of the
complete elongation complex reflects the
topology of the core transcription elongation machinery that lies at the heart of RNA
synthesis in eukaryotes and archaea.
Important questions remain. For example, it is still unclear how the DNA tunnels
affect elongation, whether the factors functionally cooperate during elongation, how
the elongation process is regulated, and
how NELF interacts with Spt4/5. Armed
with Ehara et al.’s transformative structural information, biochemists can now
test working hypotheses predicted from the
structure to pave the way for a thorough
understanding of the mechanisms of transcription elongation and pausing. j
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3. H. Eharaetal.,Science 357, 921 (2017).
4. Y. He, J. Fang, D. J. Taatjes, E. Nogales,Nature 495, 481
5. C.Plaschkaetal.,Nature 533,353(2016).
6. D.Grohmann etal.,Mol.Cell 43,263(2011).
7. S.Schulz et al., Proc. Natl. Acad. Sci. U.S.A. 113,E1816(2016).
8. A.C.M.Cheung, P.Cramer,Nature 471,249(2011).
9. K.Adelman,J. T.Lis,Genetics 13,720(2012).
10. A.Hirtreiter etal.,NucleicAcids Res. 38,4040(2010).
11. F.Werner, J. Mol. Biol.417,13(2012).
12. A. Mayeretal., Nat.Struct.Mol.Biol. 17, 1272 (2010).
13. D.Prather, N.J.Krogan,A.Emili, J.F.Greenblatt,F.Winston,
Mol. Cell. Biol. 25, 10122 (2005).
Enzymes make light work
of hydrocarbon production
An algal enzyme that uses visible light to catalyze
hydrocarbon formation may find use in biotechnology
Manchester Institute of Biotechnology, Biotechnology
and Biological Sciences Research Council/Engineering and
Physical Sciences Research Council Centre for Synthetic
Biology of Fine and Speciality Chemicals, School of Chemistry,
University of Manchester, Manchester M1 7DN, UK.
“Discovery of FAP provides
a light-dependent route to
that complements existing…