Full text of DOI:10.1080/14786419.2017.1405411

Natural Product Research
Formerly Natural Product Letters
ISSN: 1478-6419 (Print) 1478-6427 (Online) Journal homepage: http://www.tandfonline.com/loi/gnpl20
Microbial transformation of resveratrol by
endophyte Streptomyces sp. A12 isolated from
Polygonum cuspidatum
Tian Jiewei, Wang Lei, Long Xiufeng, Zhang Heming, Li Xiaoguang, Fu Haiyan
& Tian Yongqiang
To cite this article: Tian Jiewei, Wang Lei, Long Xiufeng, Zhang Heming, Li Xiaoguang,
Fu Haiyan & Tian Yongqiang (2017): Microbial transformation of resveratrol by endophyte
Streptomyces sp. A12 isolated from Polygonum cuspidatum, Natural Product Research, DOI:
10.1080/14786419.2017.1405411
To link to this article: https://doi.org/10.1080/14786419.2017.1405411
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Date: 22 November 2017, At: 05:10

Natural Product research, 2017
https://doi.org/10.1080/14786419.2017.1405411
SHORT COMMUNICATION
Microbial transformation of resveratrol by endophyte
Streptomyces sp. A12 isolated from Polygonum cuspidatum
Tian Jieweia, Wang Leia, Long Xiufenga, Zhang Heminga, Li Xiaoguanga, Fu Haiyanb and
Tian Yongqianga
aKey laboratory of leather chemistry and engineering (sichuan university), Ministry of education and college
of light Industry, textile & Food engineering, sichuan university, chengdu, china; bcollege of chemistry,
sichuan university, chengdu, china
ABSTRACT
ARTICLE HISTORY
received 4 september 2017
accepted 3 November 2017
Resveratrol (1) undergoes microbial transformation when fermented
with Streptomyces sp. A12 to yield 3, 5, 4′-trimethoxy-trans-stilbene (2).
The structure of the compound 2 was elucidated using the modern
spectroscopic techniques. This is the first report of the microbial
transformation of resveratrol to compound 2 using the endophyte
isolated from Polygonum cuspidatum.
KEYWORDS
Microbial transformation;
endophyte; Polygonum
cuspidatum; Streptomyces sp.
1. Introduction
Polygonum cuspidatum, a well-known traditional Chinese medicinal plant and a food sup-
plement (Kim et al. 2005), is officially listed in the Chinese Pharmacopoeia. The underground
part of P. cuspidatum has been used in traditional Chinese medicine for thousands of years
as a remedy for inflammation, favus, jaundice, scald and hyperlipidemia (Peng et al. 2013).
Resveratrol (3, 4′, 5 -trihydroxy-trans-stilbene) (1), a well-known natural compound with
numerous health benefits, is the main phytoconstituent of P. cuspidatum. Resveratrol pos-
sesses many pharmacological properties, including anti-inflammatory activity (Kim et al.
2005), cardio-protective (Li et al. 2012) and anticancer properties (Gupta et al. 2011). The
compound 3, 5, 4′-trimethoxy-trans-stilbene (2), a methylated derivative of resveratrol (1),
exhibited excellent anticancer activity. Unlike resveratrol, 3, 5, 4′-trimethoxy-trans-stilbene
does not exert any concentration-dependent biphasic effect on cancer cells (Calabrese
et al. 2010). Usually, the 3, 5, 4′-trimethoxy-trans-stilbene was chemically synthesised in
CONTACT tian Yongqiang
yqtian@scu.edu.cn
supplemental data for this article can be accessed at https://doi.org/10.1080/14786419.2017.1405411.
© 2017 Informa uK limited, trading as taylor & Francis Group

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T. JIEWEI ET AL.
laboratories (Aldawsari and Velázquez-Martínez 2015). Therefore, it is crucial to develop a
new biocatalytic strategy for 3, 5, 4′-trimethoxy-trans-stilbene production.
Endophytes are potential sources of novel natural products useful in the pharmaceutical
and agro-based industries (Strobel and Daisy 2003). Many endophytes can produce similar
phytochemicals alike their hosts (Strobel and Daisy 2003; Suryanarayanan et al. 2009). In this
study, we successfully isolated 37 endophytes from P. cuspidatum. One of these endophytes,
Streptomyces sp. A12, transformed resveratrol (1) to 3, 5, 4′-trimethoxy-trans-stilbene(2) pro-
duction. The structure of the compound 2 was elucidated using modern spectroscopic tech-
niques and the corresponding data were reported.
2. Results and discussion
Streptomyces sp. A12 was cultured in a 10-L fermenter containing 6 L of PDA medium for
12 days. After filtration, the mycelium was washed by EtOAc and the obtained culture was
extracted by EtOAc, concentrated and combined to obtain the crude extract. The final com-
pounds were obtained by repeated column chromatography (CC) over silica gel.
The obtained compound, 3, 5, 4′-trimethoxy-trans-stilbene (2) (Figure 1) was purified to
obtain a white powder. The molecular formula was established as C17H18O3 on the basis of
a sodium adduct ion peak at m/z 293.33 [M + Na]+ from HR-ESI-MS. The chemical structure
was further confirmed by the 1H NMR data. The 1H NMR spectrum (Figure S1) exhibited six
sets of peaks. The chemical shift δ 7.43 (d, J = 8.7 Hz, 2H) represented the resonance of two
magnetically equivalent protons of para-disubstituted phenyl ring A, and these two equiv-
alent protons were coupled to another single adjacent proton, thus appearing as a doublet
with a J-coupling value of 8.7 Hz. One doublet peak at δ 7.05 ppm corresponded to a single
proton adjacent to a double bond connecting two phenyl rings, and the large coupling
constant (J = 16.5) revealed a trans-double bond configuration. The other two doublets (one
from the phenyl ring A, the other from the double bond) overlapped each other at the region
of 7.06–6.88 ppm. The three aromatic protons of the 1, 3, 5-trisubstituted phenyl ring B
appeared at 6.66 and 6.37 ppm as two triplets, each of them having J value around 2.4 Hz,
thus denoting as meta aromatic coupling. In addition, a single peak at 3.83 ppm represented
the three CH3O groups. Therefore, the structure of the compound was ascertained as 3, 4′,
5-trimethoxy-trans-stilbene (2).
Figure 1. structures of the compounds 1 and 2.

NATURAL PRODUCT RESEARCH
3
Resveratrol (1) (Figure 1) showed concentration-dependent biphasic effects on different
cancer cell lines in vitro like, several tumour cell lines including breast, liver (Su et al. 2013),
as well as, leukemia cell lines (Calabrese et al. 2010). Resveratrol (1) inhibited cancer cell
proliferation at higher concentrations, whereas at lower concentrations the compound (1)
enhanced the cancer cell proliferation (Calabrese et al. 2010); though, this biphasic effect
was not reported for 3, 4′, 5-trimethoxy-trans-stilbene (2). Furthermore, 3, 4′, 5-trimeth-
oxy-trans-stilbene (2) demonstrated its capabilities to induce cycle arrest (Wang et al. 2010)
and apoptosis (Alex et al. 2010) by different mechanisms of action unlike resveratrol (1), and
occasionally, the compound 2 demonstrated better potency and efficacy than resveratrol
(Aldawsari and Velázquez-Martínez 2015).
3. Conclusion
In the present study, Streptomyces sp. A12 was isolated from P. cuspidatum and the endophyte
transformed resveratrol (1) to 3, 5, 4′-trimethoxy-trans-stilbene (2). Here, for the first time,
we are reporting that P. cuspidatum endophytes can bio transform resveratrol to produce 3,
5, 4′-trimethoxy-trans-stilbene.
Disclosure statement
No potential conflict of interest was reported by the authors.
Funding
This study was funded by the National Key Research and Development Program of China [grant num-
ber 2017YFB0308401]; the Key Program of Sichuan Science and Technology Project [grant number
2017GZ0430].
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