Table 1.

Summary of the descriptive characteristics of the included studies (N = 15).

Author	Country	Host Plant	Microorganisms	Fungal Identification	Growth Conditions				Enzyme Activity	Main Conclusions
					Ph	T (°C)	Agitation (rpm)	Time (days)
Mefteh et al. [20]	Tunisia	Phoenix dactylifera L.	Penicillium bilaiae	ITS-rDNA	6.26	24.5	150	ND	1086.95 U/mL	Plackett–Burman design and RSM approaches were employed for optimization of culture and environment conditions and were shown to significantly enhance protease production.
Bhagobaty and Joshi [21]	India	Potentilla fulgens	Talaromycesflavus	β-tubulin	ND	25	120	5	34.9 U/h/mL	All the endophytic fungal isolates from medicinal plant showed production of protease. The production of extracellular enzymes was greater in the liquid medium in comparison to the plate-based assays.
Elgammal et al. [22]	Egypt	Ruprechita salicifolia	Aspergillus ochraceus	18S rRNA	8	35	150	ND	292 U/mL	The protease production increased by about 7.5-fold after applying the final optimized fermentation. The partial purification results showed that the highly recovered fraction was at 60% ethanol concentration.
El-Khonezy et. al. [34]	Egypt	Ruprechita salicifolia	Aspergillus ochraceus	18S rRNA	8	35	150	6	800.1 U/mL	The enzyme was characterized as thiol-dependent serine alkaline protease. Low-cost production medium using different waste sources was applied to produce the enzyme.
Galeano et al. [23]	Brazil	Axonopus purpusii	Aspergillus niger	ITS-rDNA	ND	30	110	7	12.01 U/mL	The ability of the fungus to produce proteases might reflect the fact that these fungi have potential as biocontrol agents.
Li et al. [24]	China	Trachelospermum jasminoides	Verticillium sp.	Morphology	ND	28	160	14	3775 U/mg	Verticase is a direct degrader of fibrin clot, most probably playing a negligible role in the conversion of plasminogen to plasmin. However, for protein-based medicines, special care must be taken for an early awareness of the toxicity.
Lindstrom and Belanger [25]	United States	Poa ampla	Acremonium typhinum	ND	ND	ND	ND	ND	27 U/mL	The regulated nature of proteinase At1 suggest that its function is important in the symbiotic interaction of fungus and plants.
Matias et al. [26]	Brazil	Myrcia guianensis	Aspergillus sp.	Morphology a	5	28	150	7	3.63 U/mL	The endophytic fungus with the higher protease activity demonstrated total efficacy in the removal of the consolidated biofilm of S. aureus.
Meshram and Saxena [27]	India	Aegle marmelos	Lasiodiplodia pseudotheobromae	ITS-rDNA	ND	26	130	7	6514 U/mL	The endophytic fungus possesses potential in vitro fibrinolytic potential.
Meshram et al. [28]	India	Cathranthus roseus	Xylaria curta	28s rDNA	ND	26	130	7	34.11 U/mL	Submerged fermentation was used to produce the fibrinolytic enzyme. This protease is a novel metalloprotease possessing dual activity including direct degradation of fibrin(ogen) or by activating the tissue plasminogen.
Meshram et al. [29]	India	Cathranthus roseus	Xylaria curta	ITS-rDNA 28s rDNA	ND	28	ND	15	103.56 U/mL	The fibrinolytic enzyme xylarinase was produced by solid substrate fermentation using rice chaff medium. The purified metalloprotease showed in vitro thrombolytic activity and no cytotoxic effect.
Noor et al. [30]	Malaysia	Hibiscus	Fusarium sp.	18S rRNA a	ND	ND	ND	ND	5284 U/mL	Two fibrinolytic enzymes were purified and characterized based only on molecular weight and effect of pH and temperature.
			Penicillium citrinum	18S rRNA a	ND	ND	ND	ND	2200 U/mL
Rajput et al. [31]	India	Cupressus torulosa D. Don	Alternaria alternata	Morphology	7	27	ND	2	162 U/mL	The fungus can be industrially exploited for the synthesis of protease and strain improvement studies can be carried out to enhance enzyme production.
Wu et al. [32]	China	Chrysanthemum	Fusarium sp.	ITS	ND	28	220	6	137,000 U	The fibrinolytic enzyme, named Fu-P, was purified and identified as a chymotrypsin-like serine metalloprotease. May be a potential candidate for thrombolytic therapy or thrombosis prevention.
Zaferanloo et al. [33]	Australia	Eremophilia longifolia.	Alternaria alternata	Morphology ITS	6.5	30	ND	7	69.86 BAEE units/mg	The protease can be applied to cheese making and in milk-clotting where the fermentation conditions are suitable to the activation of protease

^a Data presented in earlier studies referenced in the article. ND: No data.