NATURAL PROꢂUCT RꢁSꢁARCH
3
1
with the H spectra of synthetic standards (Figure S2). To our knowledge, this is the first time
that both compounds have been isolated from S. sp strain 22-4. As several cyclic dipeptides
have been previously reported from production broths (Prasad 1995), the medium alone
was extracted and carefully investigated by HPLC to confirm that neither cyclo(l-Pro-l-Tyr)
or cyclo(d-Pro-l-Tyr) were present.
2
.2. Antibacterial activity against plant pathogenic bacteria
Previously, both cyclo(l-Pro-l-Tyr) and cyclo(d-Pro-l-Tyr) have been isolated from several
and antibacterial activities (Nishanth Kumar et al. 2012; Tommonaro et al. 2012; Kumar et al.
2013). To the best of our knowledge, this is the first time that the cyclo(d-Pro-l-Tyr) has been
isolated from Streptomyces. ꢂue to the antimicrobial activity of both cyclo(l-Pro-l-Tyr) and
cyclo(d-Pro-l-Tyr), this led us to assess the biological activity on untested phytopathogenic
bacteria. Bacterial wilt and canker in particular are important diseases in commercial crop
plants, causing significant economic losses worldwide. In this work, both cyclo(l-Pro-l-Tyr)
and cyclo(d-Pro-l-Tyr) were tested against Xanthomonas axonopodis pv. citri, Ralstonia sola-
nacearum and Clavibacter michiganensis. X. axonopodis pv. citri is an extremely persistent
causative agent of bacterial canker in citrus (Brunings & Gabriel 2003), whilst R. solanacearum
Gleason et al. 1993). Both compounds exhibited activity against X. axonopodis pv. citri and
R. solanacearum, albeit weak (MIC 31.25 μg/mL) when compared to standard antibacterial
agents (Table 1). No antibacterial activity was observed against C. michiganensis even at
relatively high concentrations (up to 500 μg/mL).
Although there is currently a small trade-off with potency, the broad spectrum of antimi-
crobial activity of cyclo(
l-Pro-
l-Tyr) and cyclo(
d
-Pro- -Tyr) however means these compounds
l
may have potential for use as agricultural biocontrol agents. This can be seen from a chiti-
nase-producing Streptomyces glauciniger WICC-A03 (Awad et al. 2014) or a related compound,
cyclo(4-hydroxy-
l
-Pro- -Trp), which has already been deployed as a non-toxic biopreservative
l
agent to inhibit the growth of A. flavus and A. niger on peanut kernels (Kumar et al. 2014).
With further toxicity testing and structure modification to improve the biological activity
of cyclo(Pro-Tyr), this cyclic dipeptide may be a promising biocontrol agent for use in the
agricultural industry.
3
. Experimental
ꢁxperimental information is provided in Supplementary material.
4
. Conclusion
This is the first time that both cyclo(l-Pro-l-Tyr) and cyclo(d-Pro-l-Tyr) were isolated from
S. sp. strain 22-4 and we are the first to show their antibacterial activity against economically
phytopathogenic bacteria X. axonopodis pv. citri and R. Solanacearum. With the use of toxic
chemicals in agricultural industry to prevent the crop damage, the use of cyclic dipeptides
as biological control agents may provide a sustainable approach to improve the crop quality
without damaging the environment or human health.